Outcome Measures in Adult Vulvar Lichen Sclerosus: A Case Series of Women Diagnosed as Juveniles.

OBJECTIVES: Studies on the consequences of juvenile vulvar lichen sclerosus (JVLS) in adulthood are limited. A number of measuring tools are available for analyzing adult vulvar lichen sclerosus (VLS), but these have not been applied in studies on JVLS. The aim is to study physical findings, quality of life, sexual well-being, and self-image in adult women with a history of juvenile VLS. MATERIALS AND METHODS: Adult women with a biopsy proven history of JVLS were recruited to be examined and surveyed using available standardized measurement tools. This took place in an outpatient setting by physicians who were not involved in the treatment of participants. RESULTS: Twenty-seven women (median age 29 years) with a history of JVLS and median time since biopsy of 19.5 years were recruited. Of these women, 59% currently had symptoms, 63% had signs of active disease, and 85% had moderate to severe architectural changes. Despite these residual signs, vulvar specific-quality of life and vulvar self-image scored favorably while generic health-related quality of life was somewhat effected. CONCLUSIONS: JVLS has consequences in adulthood involving physical findings and vulvar quality of life. The use of standardized outcome measures for clinical practice and research purposes facilitates a better understanding of the sequelae to JVLS.

Outcome Measures in Adult Vulvar Lichen Sclerosus: A Systematic Review.

OBJECTIVES: Core outcome domains (CODs) for treatment of adult vulvar lichen sclerosus (VLS) have recently been established through a Delphi study. A number of measuring tools are available for evaluating VLS. The aim of this study is to identify available standardized measurement tools for the major CODs for VLS that have recently been defined, namely, physical findings and quality of life (QoL) specific to VLS. MATERIALS AND METHODS: A systematic search through September 8, 2023, for measuring tools applicable to VLS regarding physical findings and QoL including sexual function or sexual well-being and self-image was performed. RESULTS: Thirty-five studies were included in the systematic review describing 26 tools covering the following 6 outcome domains: QoL-general health, QoL-lichen sclerosus specific, symptoms, clinical signs, emotional impact, and sexual functioning. CONCLUSIONS: In current research, there is no uniformity in use of measurement tools for evaluating VLS. The established CODs to evaluate treatment of VLS are applicable for evaluating disease course as well. A comprehensive study to reach consensus regarding measurement of physical findings, QoL-lichen sclerosus specific, sexuality, and self-image taking the predetermined CODs and other factors such as age into account is needed.

Growing up with juvenile vulvar lichen sclerosus, the experiences and care needs of adult women with lichen sclerosus since childhood: a qualitative exploration.

BACKGROUND: Vulvar Lichen Sclerosus (VLS) is a chronic remitting condition affecting the genital skin of females of all ages. Although qualitative studies have been conducted focusing on women with VLS in mid-life or older, less is known about the experiences of individuals with VLS from childhood or adolescence onward. OBJECTIVE: To gain understanding of the experiences of women with a history of juvenile VLS (JVLS) regarding the impact of the disease on their personal lives, and their experiences and needs regarding care and guidance. METHODS: A qualitative study was conducted consisting of 27 in-depth face-to-face interviews with adult women with a histologically confirmed history of JVLS, striving for maximum variation and saturation. Interviews were audio-taped and transcribed verbatim. A thorough thematic content analysis was performed. RESULTS: Three main themes were identified. I. Varying impact of living with JVLS: Women experienced diverse emotional and physical impact, from shame and denial to complete acceptance, from restrictions in daily functioning to no limitations. They felt hindered by their own lack of knowledge about JVLS, and generally expressed a positive influence of sharing their experiences with people close to them. II. Finding one's way in care and guidance: While navigating care and guidance, women often felt hindered by knowledge gaps among health care professionals (HCPs), lack of continuity in care and guidance, lack of life-stage adjusted and future-oriented information provision, inadequate guidance around life events, and insufficient monitoring of determinants of therapy adherence. III. Need for patient-tailored care: Patients stressed the need for age-appropriate and life-phase adjusted information, guidance around life-events and compassionate contact with knowledgeable HCPs, aware of the determinants of therapy adherence and influencing factors. CONCLUSIONS: Age-appropriate life-phase adjusted individually tailored care for women diagnosed with VLS in childhood or adolescence is needed. Care and guidance from childhood onward should encompass a standard of care adapted to the individual as needs change over time. This involves taking interpersonal differences into account, including differences in support network and coping strategies. These findings demonstrate the need for improving awareness and knowledge about (J)VLS among HCPs, especially primary care providers, and among the general public.

Long-term consequences of juvenile vulvar lichen sclerosus: A cohort study of adults with a histologically confirmed diagnosis in childhood or adolescence.

INTRODUCTION: Vulvar lichen sclerosus (VLS) occurs in at least one in 900 girls. There is limited knowledge as to what extent the disease persists in adulthood and what the repercussions in adulthood may be. The aim of this study is to evaluate the long-term consequences of VLS diagnosed in childhood or adolescence. MATERIAL AND METHODS: The population of females histologically diagnosed with VLS in childhood or adolescence in the Netherlands between 1991 and 2015 was identified through the national pathology database. Histological specimens were retrieved and re-evaluated. Potential participants for whom the diagnosis was reconfirmed and who are now adults, were then traced and surveyed. Descriptive statistics were calculated and compared with the literature. Main outcome measures are the demographics of the cohort, their scores on standardized quality of life (QoL) and sexuality questionnaires and answers to additional questions regarding patients' experience with the disease. The questionnaires used were the Dermatology Life Quality Index (DLQI), the Skindex-29, the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale-Revised (FSDS-R). Secondary outcome measures include obstetric history and histological features found in the original tissue specimens. RESULTS: A total of 81 women participated, median age 29.0 years, median follow-up from childhood diagnosis 19.5 years. Both QoL and sexuality were somewhat affected in 51.9% of cases. Less than half (45%) reported having regular check-ups. Forty-five (56%) reported symptoms within the past year; of those with symptoms, 14 (31%) were not under surveillance. Cesarean section rate (14.5%) was comparable to the general population, and there were more high-grade obstetric anal sphincter injuries with vaginal deliveries than expected. Sixteen respondents (20%) were not aware of the childhood diagnosis prior to this study. CONCLUSIONS: Symptoms due to VLS are reported by most adults diagnosed as juveniles. QoL and sexuality are affected and correlate to recent symptoms. VLS as a juvenile does not preclude a vaginal delivery. Women diagnosed with VLS in childhood or adolescence are often lost to follow-up.

Evaluation of a Web-Based Intervention for Patients with Gestational Trophoblastic Disease: A Randomized Controlled Trial.

OBJECTIVE: Gestational trophoblastic diseases (GTD) comprise a group of rare diseases originating from the trophoblast affecting women of childbearing age. Providing optimal information to patients with a rare disease is challenging because of the small number of patients and limited clinical expertise of many healthcare professionals. Both knowledge and lack of knowledge in patients may influence illness perception. We investigated whether a web-based interactive intervention influences illness perception and knowledge in women with GTD. DESIGN: This was a multicenter randomized control trial conducted at general and academic hospitals in the Netherlands, including newly diagnosed GTD patients between 2017 and 2019. METHODS: Sixty-nine patients were randomized between direct access or postponed access to an online tool on GTD and received online questionnaires about illness perception, knowledge, and anxiety. The main outcome measures were illness perception (primary outcome measure) and knowledge (secondary outcome measure). RESULTS: Patients using the online tool were satisfied with the information from the tool (92%). Although they had a higher level of knowledge compared to the control group (p = 0.006), illness perception did not change. Also, no differences in levels of anxiety, depression, or distress were observed between the groups. LIMITATIONS: Participants had access to other information sources and many searched other websites. It is unknown what kind of websites were visited and when. It is unknown if the increased knowledge levels and low levels of distress will sustain over time as no long term follow-up took place. Healthcare professionals were not interviewed on how they experienced the consultation before and after using the tool by the patients. CONCLUSIONS: The online tool did not change illness perception but was shown to be valuable for newly diagnosed GTD patients to gain knowledge. The improvement in knowledge after digital education indicates that this tool can be used as an effective method of supporting GTD patients' informational needs without causing extra distress. TWEETABLE ABSTRACT: A web-based tool for trophoblastic disease does not change illness perception of patients but is valuable to gain knowledge.

The long-term clinical consequences of juvenile vulvar lichen sclerosus: A systematic review.

BACKGROUND: Vulvar lichen sclerosus (VLS) occurring in children and adolescents may have repercussions throughout life. OBJECTIVE: We sought to assess the evidence available on the long-term consequences of juvenile VLS. METHODS: Multiple databases were searched for studies containing long-term follow-up information on children or adolescents up to age 18 years with VLS. Articles were classified by level of evidence and the specific aspects of VLS studied. RESULTS: In all, 37 studies met the inclusion criteria, giving information on the long-term consequences of VLS, of which 13 were cohort studies and 24 were case reports or series. These publications show that signs and symptoms persist after puberty and beyond, scarring and permanent architectural changes occur, treatment is effective with regard to symptoms, and long-term quality of life is affected. Findings suggest a possible relationship with risk of malignancy. The included publications had low-level evidence. LIMITATIONS: Meta-analysis was not possible because the studies had different focuses. Very few patients were followed into adulthood. CONCLUSIONS: There is low-level evidence suggesting long-term repercussions of juvenile VLS. Studies following children and adolescents with VLS into adulthood are needed to better understand the course of this disease and its repercussions on adult vulvar health.

Group Assessment of Resident Performance: Valuable for Program Director Judgment?

BACKGROUND: Group discussion of resident performance is an emerging assessment approach in postgraduate medical education. However, groups do not necessarily make better decisions than individuals. OBJECTIVE: This study examined how group meetings concerning the assessment of residents take place, what information is shared during the meetings, and how this influences program directors' judgment of resident performance. METHODS: In 2017, the researchers observed 10 faculty group meetings where resident performance was discussed and interviewed the program directors within a month after the meetings. We used a thematic framework analysis to identify themes from the transcribed meetings and interviews. RESULTS: The information shared by group members during the meetings had 2 aims: (1) forming a judgment about the residents, and (2) faculty development. Most group members shared information without written notes, most discussions were not structured by the program director, the major focus of discussions was on residents with performance concerns, and there was a lack of a shared mental model of resident performance. The program directors who benefited most from the meetings were those who thought group members were engaged and summarized the information after every discussion. CONCLUSIONS: Unstructured discussions and a lack of a shared mental model among group members impede effective information sharing about resident performance with a developmental approach. Structured discussions with an equal amount of discussion time for every resident and creating a shared mental model about the purpose of the discussions and the assessment approach could enhance use of a developmental approach to assessing resident performance.

Using conversation analysis to explore feedback on resident performance.

Feedback on clinical performance of residents is seen as a fundamental element in postgraduate medical education. Although literature on feedback in medical education is abundant, many supervisors struggle with providing this feedback and residents experience feedback as insufficiently constructive. With a detailed analysis of real-world feedback conversations, this study aims to contribute to the current literature by deepening the understanding of how feedback on residents' performance is provided, and to formulate recommendations for improvement of feedback practice. Eight evaluation meetings between program directors and residents were recorded in 2015-2016. These meetings were analyzed using conversation analysis. This is an ethno-methodological approach that uses a data-driven, iterative procedure to uncover interactional patterns that structure naturally occurring, spoken interaction. Feedback in our data took two forms: feedback as a unidirectional activity and feedback as a dialogic activity. The unidirectional feedback activities prevailed over the dialogic activities. The two different formats elicit different types of resident responses and have different implications for the progress of the interaction. Both feedback formats concerned positive as well as negative feedback and both were often mitigated by the participants. Unidirectional feedback and mitigating or downplaying feedback is at odds with the aim of feedback in medical education. Dialogic feedback avoids the pitfall of a program director-dominated conversation and gives residents the opportunity to take ownership of their strengths and weaknesses, which increases chances to change resident behavior. On the basis of linguistic analysis of our real-life data we suggest implications for feedback conversations.

Design and evaluation of a clinical competency committee.

INTRODUCTION: In postgraduate medical education, group decision-making has emerged as an essential tool to evaluate the clinical progress of residents. Clinical competency committees (CCCs) have been set up to ensure informed decision-making and provide feedback regarding performance of residents. Despite this important task, it remains unclear how CCCs actually function in practice and how their performance should be evaluated. METHODS: In the prototyping phase of a design-based approach, a CCC meeting was developed, using three theoretical design principles: (1) data from multiple assessment tools and multiple perspectives, (2) a shared mental model and (3) structured discussions. The meetings were held in a university children's hospital and evaluated using observations, interviews with CCC members and an open-ended questionnaire among residents. RESULTS: The structured discussions during the meetings provided a broad outline of resident performance, including identification of problematic and excellent residents. A shared mental model about the assessment criteria had developed over time. Residents were not always satisfied with the feedback they received after the meeting. Feedback that had been provided to a resident after the first CCC meeting was not addressed in the second meeting. DISCUSSION: The principles that were used to design the CCC meeting were feasible in practice. Structured discussions, based on data from multiple assessment tools and multiple perspectives, provided a broad outline of resident performance. Residency programs that wish to implement CCCs can build on our design principles and adjust the prototype to their particular context. When running a CCC, it is important to consider feedback that has been provided to a resident after the previous meeting and to evaluate whether it has improved the resident's performance.

Judging residents' performance: a qualitative study using grounded theory.

BACKGROUND: Although program directors judge residents' performance for summative decisions, little is known about how they do this. This study examined what information program directors use and how they value this information in making a judgment of residents' performance and what residents think of this process. METHODS: Sixteen semi-structured interviews were held with residents and program directors from different hospitals in the Netherlands in 2015-2016. Participants were recruited from internal medicine, surgery and radiology. Transcripts were analysed using grounded theory methodology. Concepts and themes were identified by iterative constant comparison. RESULTS: When approaching semi-annual meetings with residents, program directors report primarily gathering information from the following: assessment tools, faculty members and from their own experience with residents. They put more value on faculty's comments during meetings and in the corridors than on feedback provided in the assessment tools. They are influenced by their own beliefs about learning and education in valuing feedback. Residents are aware that faculty members discuss their performance in meetings, but they believe the assessment tools provide the most important proof to demonstrate their clinical competency. CONCLUSIONS: Residents think that feedback in the assessment tools is the most important proof to demonstrate their performance, whereas program directors scarcely use this feedback to form a judgment about residents' performance. They rely heavily on remarks of faculty in meetings instead. Therefore, residents' performance may be better judged in group meetings that are organised to enhance optimal information sharing and decision making about residents' performance.

Is there uniformity in definitions and treatment of gestational trophoblastic disease in Europe?

OBJECTIVES: Because gestational trophoblastic disease is rare, little evidence is available from randomized controlled trials on optimal treatment and follow-up. Treatment protocols vary within Europe, and even between different centers within countries. One of the goals of the European Organization for Treatment of Trophoblastic Diseases (EOTTD) is to harmonize treatment in Europe. To provide a basis for international standardization of definitions, treatment and follow-up protocols in gestational trophoblastic disease, we evaluated differences and similarities between protocols in EOTTD countries. METHODS: Members from each EOTTD country were asked to complete an online structured questionnaire comprising multiple-choice and multiple-answer questions. The following themes were discussed: incidence of gestational trophoblastic disease and gestational trophoblastic neoplasia, definitions, guidelines, classification system, treatment, recurrence, and follow-up. RESULTS: Forty-four respondents from 17 countries participated in this study. Guidelines were present in 80% of the countries and the FIGO (Fédération Internationale de Gynécologie et d'Obstétrique) staging and risk classification was often used to estimate risks. Agreement about when to start chemotherapy for post-molar gestational trophoblastic neoplasia was present among 66% of the respondents. Preferred first-line treatments in low- and high-risk gestational trophoblastic neoplasia were methotrexate (81%) and EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) (93%), respectively. The definition of human chorionic gonadotropin normalization after hydatidiform mole evacuation was two consecutive normal values for nine countries. The FIGO definition of post-molar gestational trophoblastic neoplasia based on human chorionic gonadotropin plateau or rise was agreed on by 69% of respondents, and only 69% and 74% defined low-risk and high-risk disease, respectively, using FIGO criteria. There were major differences in definitions of recurrence, chemotherapy resistance and follow-up protocols among countries, despite EOTTD consensus statements. CONCLUSIONS: This questionnaire provides a good overview of current clinical practices in different countries. Based on the survey results, it is clear that there are several gestationaltrophoblastic disease-related topics that need urgent attention within the EOTTD community to create more uniformity and to aid the development of uniform guidelines in Europe.

Sexual response in women with Mayer-Rokitansky-Küster-Hauser syndrome with a nonsurgical neovagina.

BACKGROUND: Sexual dysfunction is prevalent in women with Mayer-Rokitansky-Küster-Hauser syndrome after the creation of a neovagina. Insight into the physiologic response of the neovagina during sexual arousal is lacking, although this would help in the understanding of sexual function of these patients. The physiologic sexual response of the vagina can be measured objectively by vaginal photoplethysmography to assess vaginal blood flow. OBJECTIVE: Testing whether the physiologic and subjective sexual response in women with Mayer-Rokitansky-Küster-Hauser syndrome with a neovagina differs from the response in women with a natal vagina. STUDY DESIGN: Vaginal blood flow (vaginal pulse amplitude) and subjective sexual responses during neutral and erotic film viewing were assessed in premenopausal women with Mayer-Rokitansky-Küster-Hauser syndrome with a nonsurgically created neovagina (n=15) and were compared with responses of an age-matched control group (n=21). RESULTS: All women with Mayer-Rokitansky-Küster-Hauser syndrome had created their neovagina themselves by dilation. Women with Mayer-Rokitansky-Küster-Hauser syndrome showed a significantly smaller vaginal pulse amplitude compared with control subjects during neutral film viewing (P=.002). In both groups, vaginal pulse amplitude increased significantly during erotic film viewing, but this increase was significantly smaller in the Mayer-Rokitansky-Küster-Hauser syndrome group (P<.005). Levels of subjective sexual arousal did not significantly differ between the 2 groups (P>.2). CONCLUSION: Women with Mayer-Rokitansky-Küster-Hauser syndrome with a nonsurgically created neovagina showed a weaker vaginal blood flow response during visual sexual stimulation and poorer basal blood flow compared with control subjects. The differences in vaginal blood flow may be related to less vascularization and innervation of the neovagina compared with the natal vagina. The weaker vaginal sexual response can play a role in sexual dysfunction; however, despite the weaker vaginal response, women with Mayer-Rokitansky-Küster-Hauser syndrome did not differ in their level of subjective sexual arousal. Future studies may compare vaginal blood flow and subjective sexual response of women with Mayer-Rokitansky-Küster-Hauser syndrome with nonsurgically and surgically created vaginas.

Wish to conceive and concerns to develop cardiovascular complications during pregnancy in patients with Turner syndrome.

INTRODUCTION: Turner syndrome (TS) is associated with subfertility and infertility. Nevertheless, an increasing number of women become pregnant through oocyte donation. The wish to conceive may be negatively influenced by the fear of cardiovascular complications. The aim was to investigate the wish to conceive and the concerns about cardiovascular complications during pregnancy in women with TS. METHODS: The patient association for TS invited all members of ≥18 years old (n = 344) to complete a specifically developed, disease-specific questionnaire, including questions about fertility, wish to conceive, attempts and concerns. Results were compared with previously published results of this questionnaire in women with congenital heart disease. RESULTS: The questionnaire was completed by 89 women (median age 30.1 years, Q1-Q3 = 22.9-39.4). Of them, 51% had 45, X0-monosomy and 38% had ≥1 cardiac abnormality. Seventeen women (19%) had attempted to become pregnant and 12 of them succeeded to become pregnant. Women who had not undertaken attempts to conceive (81%), considered themselves mainly too young or had no partner. Of the total sample, 58% were concerned about the influence of pregnancy on their cardiovascular status. This was higher (75%) in the sample of women with TS and cardiac abnormalities, than in women with congenital heart disease from a previously published cohort (21%), (p < .001). There were no differences in concerns about pregnancy complications between women with TS who respectively had or had not attempted to become pregnant. DISCUSSION: Women with TS, especially those with cardiac abnormalities, show serious concerns about the risks pregnancy may have. Patients should be timely counseled and specifically asked about their concerns. Psychosocial care should be provided when necessary.

Earlier diagnosis and serum human chorionic gonadotropin regression in complete hydatidiform moles.

OBJECTIVE: To estimate serum human chorionic gonadotropin (hCG) regression in uneventful complete hydatidiform moles before and after the introduction of routine first-trimester ultrasonography. METHODS: Gestational age, maternal age, preevacuation hCG concentrations, serum hCG regression, and hCG disappearance time among a recent group of 137 women with uneventful complete hydatidiform moles that were found between 1994 and 2006 were evaluated retrospectively and compared with a historical cohort of 106 patients with complete moles that were found between 1977 and 1989. RESULTS: Gestational age, preevacuation hCG concentration, and hCG disappearance time were significantly lower in the recent complete hydatidiform mole cohort compared with the historic series. Ninety-nine percent of the recent cohort achieved hCG normalization within 19 weeks after uterine evacuation compared with 25 weeks in the historic group. CONCLUSION: Earlier serum hCG regression in the recent cohort of complete hydatidiform moles probably is a result of widely used first-trimester ultrasonography leading to detection and evacuation of complete moles at younger gestational ages, resulting in lower hCG levels at time of evacuation. LEVEL OF EVIDENCE: : II.

Acute type A aortic dissection complicating pregnancy at 32 weeks: surgical repair after cesarean section.

A 40-year-old, gravida 2, para 1 woman presented at a gestational age of 32 + 5 weeks' with sudden onset of a sharp chest and thoracic back pain. She was admitted 1 hour before the onset of pain because of some minor postcoital vaginal blood loss. Pregnancy was uneventful until 30 weeks of pregnancy when mild gestational diabetes was diagnosed. Computer tomography demonstrated a type A aortic dissection. A healthy male infant of 2105 g was delivered by emergency cesarean section followed by a Bentall procedure with composite graft replacement of the aorta, and aortic valve replacement was performed. Rapid multidisciplinary consultation, collaboration, and quick decision making led to a successful outcome for both the mother and her child.

Anti-Mullerian hormone, inhibin B, and antral follicle count in young women with ovarian failure.

CONTEXT: Ovarian dysfunction is classically categorized on the basis of cycle history, FSH, and estradiol levels. Novel ovarian markers may provide a more direct insight into follicular quantity in hypergonadotropic women. OBJECTIVE: The objective of the study was to investigate the distribution of novel ovarian markers in young hypergonadotropic women as compared with normogonadotropic regularly menstruating women. DESIGN: This was a nationwide prospective cohort study. SETTING: The study was conducted at 10 hospitals in The Netherlands. PATIENTS: Women below age 40 yr with regular menses and normal FSH (controls; n = 83), regular menstrual cycles and elevated FSH [incipient ovarian failure (IOF); n = 68]; oligomenorrhea and elevated FSH [referred to as transitional ovarian failure (TOF); n = 79]; or at least 4 months amenorrhea together with FSH levels exceeding 40 IU/liter [premature ovarian failure (POF); n = 112]. MAIN OUTCOME MEASURES: Serum levels of anti-Müllerian hormone (AMH), inhibin B, and antral follicle count (AFC) was measured. RESULTS: All POF patients showed AMH levels below the fifth percentile (p(5)) of normoovulatory women. Normal AMH levels (>p(5)) could be identified in 75% of IOF, 33% of TOF patients, and 98% of controls. AFC and AMH levels changed with increasing age (P < 0.0001), whereas inhibin B did not (P = 0.26). AMH levels were significantly different between TOF and IOF over the entire age range, whereas AFC became similar for TOF and IOF at higher ages. CONCLUSIONS: Compared with inhibin B and AFC, AMH was more consistently correlated with the clinical degree of follicle pool depletion in young women presenting with elevated FSH levels. AMH may provide a more accurate assessment of the follicle pool in young hypergonadotropic patients, especially in the clinically challenging subgroups of patients with elevated FSH and regular menses (i.e. IOF) and in hypergonadotropic women with cycle disturbances not fulfilling the POF diagnostic criteria (i.e. TOF).

Treatment and prognosis of post term choriocarcinoma in The Netherlands.

INTRODUCTION: Antecedent term pregnancy is an adverse prognostic factor in Gestational Trophoblastic Disease (GTD). In The Netherlands, patients with post term choriocarcinoma are considered high-risk independent of WHO score. In the present study, we assessed whether post term choriocarcinoma always has to be considered high-risk, requiring first line treatment with combination chemotherapy, or whether a subgroup of patients is distinguishable in which single-agent Methotrexate is a safe alternative. PATIENTS AND METHODS: The study is a retrospective multicenter cohort study. Patients registered by the Dutch Working Party on Trophoblastic Disease between 1986 and 2004 with choriocarcinoma after a non-molar pregnancy were eligible. Hospital and outpatient records of the patients were reviewed. RESULTS: In total, 68 patients with non-molar choriocarcinoma were registered of whom 44 had an antecedent term pregnancy. Most post term patients (77%) were high-risk according to the WHO staging system. The majority of patients presented with metrorraghia and high hCG levels. Lung and liver metastases were common (respectively 64% and 28%), probably caused by a delay in diagnosis (median interval 16 weeks). Patients were often Methotrexate-resistant (75%). Overall survival was 86% in patients with a post term choriocarcinoma. CONCLUSIONS: Although term pregnancy is an adverse prognostic factor in GTD, current survival is comparable to the general survival in high-risk patients. A subgroup of patients in which monotherapy would be sufficient could not be identified. Immediate administration of combination chemotherapy seems justified, even in those few cases when scoring systems would suggest low- or medium-risk disease.

Early identification of resistance to first-line single-agent methotrexate in patients with persistent trophoblastic disease.

PURPOSE: A generally accepted definition for resistance to first-line single-agent chemotherapy for persistent trophoblastic disease (PTD) is lacking. In the present study, a normogram for serum human chorionic gonadotropin (hCG) from patients with normalization of serum hCG after first-line single-agent chemotherapy for PTD was constructed to identify patients resistant to this chemotherapy. PATIENTS AND METHODS: Between 1987 and 2004, data from 2,132 patients were registered at the Dutch Central Registry for Hydatidiform Moles. A normal serum hCG regression corridor was constructed for 79 patients with low-risk PTD who were cured by single-agent methotrexate (MTX) chemotherapy (control group). Another group of 29 patients with low-risk PTD needed additional alternative therapies (dactinomycin and multiagent chemotherapy) for failure of serum hCG to normalize with single-agent chemotherapy (study group). RESULTS: Serum hCG measurement preceding the fourth and sixth single-agent chemotherapy course proved to have excellent diagnostic accuracy for identifying resistance to single-agent chemotherapy, with an area under the curve (AUC) for receiver operating characteristic curve analysis of 0.949 and 0.975, respectively. At 97.5% specificity, serum hCG measurements after 7 weeks showed 50% sensitivity. CONCLUSION: In the largest study to date, we describe the regression of serum hCG levels in patients with low-risk PTD successfully treated with MTX. At high specificity, hCG levels in the first few courses of MTX can identify half the number of patients who are extremely likely to need alternative chemotherapy to cure their disease and for whom further treatment with single-agent chemotherapy will be ineffective.

Influence of oral contraceptive pills on phenotype expression in women with polycystic ovary syndrome.

Polycystic ovarian syndrome (PCOS) is characterized by a heterogeneous phenotype including chronic anovulation, hyperandrogenism and polycystic ovaries. The use of oral contraceptive pills (OCP) alters features characteristic for the syndrome. In the present study, PCOS features were compared between women using or not using OCP at the time of the study. One hundred and one women diagnosed with normogonadotrophic anovulatory infertility were included. A total of 81 (80%) women were diagnosed with PCOS (revised 2003 criteria). From these women, a total of 54 did not use OCP, whereas 27 women did. Corrected for age, women taking OCP had increased serum concentrations of sex hormone-binding globulin (P < 0.001). Serum concentrations of testosterone (P = 0.04) and androstenedione (P = 0.01) were decreased. These differences resulted in a decreased free androgen index for women currently taking OCP compared with women without (P < 0.001). The mean ovarian volume/ovary and the mean follicle number/ovary were not different. Use of OCP influences phenotype expression (the observable trait) of individual women known to suffer from PCOS by reducing hyperandrogenism. Despite taking OCP, women still fulfilled the revised 2003 criteria for the syndrome, as PCO morphology was still present. Hence, OCP use does not appreciably affect the PCOS phenotype.

Feasibility of central co-ordinated EMA/CO for gestational trophoblastic disease in the Netherlands.

OBJECTIVE: In the Netherlands, high risk gestational trophoblastic disease (GTD) patients are treated in different referral hospitals with a national working party on trophoblastic tumours having a co-ordinating function. Our purpose was to evaluate whether this policy is a satisfactory alternative to complete centralisation. DESIGN: A retrospective study of all etoposide, methotrexate, actomycin D, cyclophosphamide and vincristine (EMA/CO)-treated women in the Netherlands between 1986 and 1997. Data regarding risk factors, treatment results and toxicity were collected. SETTING: Ten hospitals; 2 general, 6 academical and 2 oncology centres. POPULATION: Fifty EMA/CO-treated women registered by the central registration unit of the Dutch Working Party on Trophoblastic Disease. METHODS: Patients files and quarterly reports of the Dutch Working Party. MAIN OUTCOME MEASURES: Cure rate and consistency of treatment in different hospitals. RESULTS: EMA/CO treatment was administered in 10 different hospitals. All patients were discussed during the meetings of the Dutch Working Party and overall, 86% of patients were cured. Consistency in treatment was good. CONCLUSIONS: Cure rates were comparable with results of single institution series. We conclude that treatment of high risk GTD patients in different referral hospitals with concentration of expertise in a working party is a good alternative to centralisation of treatment in GTD specialised hospitals.