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.

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.

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.

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.

Risk of cancer in children and young adults conceived by assisted reproductive technology.

STUDY QUESTION: Do children conceived by ART have an increased risk of cancer? SUMMARY ANSWER: Overall, ART-conceived children do not appear to have an increased risk of cancer. WHAT IS KNOWN ALREADY: Despite the increasing use of ART, i.e. IVF or ICSI worldwide, information about possible long-term health risks for children conceived by these techniques is scarce. STUDY DESIGN, SIZE, DURATION: A nationwide historical cohort study with prospective follow-up (median 21 years), including all live-born offspring from women treated with subfertility treatments between 1980 and 2001. PARTICIPANTS/MATERIALS, SETTING, METHODS: All offspring of a nationwide cohort of subfertile women (OMEGA study) treated in one of the 12 Dutch IVF clinics or two fertility clinics. Of 47 690 live-born children, 24 269 were ART-conceived, 13 761 naturally conceived and 9660 were conceived naturally or through fertility drugs, but not by ART. Information on the conception method of each child and potential confounders were collected through the mothers' questionnaires and medical records. Cancer incidence was ascertained through linkage with The Netherlands Cancer Registry from 1 January 1989 until 1 November 2016. Cancer risk in ART-conceived children was compared with risks in naturally conceived children from subfertile women (hazard ratios [HRs]) and with the general population (standardized incidence ratios [SIRs]). MAIN RESULTS AND THE ROLE OF CHANCE: The median follow-up was 21 years (interquartile range (IQR): 17-25) and was shorter in ART-conceived children (20 years, IQR: 17-23) compared with naturally conceived children (24 years, IQR: 20-30). In total, 231 cancers were observed. Overall cancer risk was not increased in ART-conceived children, neither compared with naturally conceived children from subfertile women (HR: 1.00, 95% CI 0.72-1.38) nor compared with the general population (SIR = 1.11, 95% CI: 0.90-1.36). From 18 years of age onwards, the HR of cancer in ART-conceived versus naturally conceived individuals was 1.25 (95% CI: 0.73-2.13). Slightly but non-significantly increased risks were observed in children conceived by ICSI or cryopreservation (HR = 1.52, 95% CI: 0.81-2.85; 1.80, 95% CI: 0.65-4.95, respectively). Risks of lymphoblastic leukemia (HR = 2.44, 95% CI: 0.81-7.37) and melanoma (HR = 1.86, 95% CI: 0.66-5.27) were non-significantly increased for ART-conceived compared with naturally conceived children. LIMITATIONS, REASONS FOR CAUTION: Despite the large size and long follow-up of the cohort, the number of cancers was rather small for subgroup analyses as cancer in children and young adults is rare. WIDER IMPLICATIONS OF THE FINDINGS: Overall, ART-conceived children do not appear to have an increased cancer risk after a median follow-up of 21 years. This large study provides important results, enabling physicians to better inform couples considering ART about the long-term safety of ART for their children. However, larger studies with prolonged follow-up are needed to investigate cancer risk in adults and in children conceived by ICSI and/or from cryopreserved embryos. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by The Dutch Cancer Society (NKI 2006-3631) which funded the OMEGA-women's cohort and Children Cancer Free (KIKA;147) which funded the OMEGA-offspring cohort. We declare no competing interests.

Risk of Colorectal Cancer After Ovarian Stimulation for In Vitro Fertilization.

BACKGROUND & AIMS: Apart from lifestyle factors, sex hormones also seem to have a role in the etiology of colorectal cancer. This raises interest in the possible effects of fertility drugs, especially because the use of ovarian stimulation for in vitro fertilization (IVF) has strongly increased over the past decades. METHODS: In 1996, a nationwide cohort study was set up to examine cancer risk in a population that included 19,158 women who received ovarian stimulation for IVF (IVF group) and 5950 women who underwent subfertility treatments other than IVF (non-IVF group). Cancer incidence was ascertained through linkage with the Netherlands Cancer Registry. Colorectal cancer risk in the IVF group was compared with those in the general population and in the non-IVF group. RESULTS: After a median follow-up of 21 years, 109 colorectal cancers were observed. Compared with the general population, risk of colorectal cancer was not increased in the IVF group (standardized incidence ratio, 1.00; 95% confidence interval [CI], 0.80-1.23), and was significantly decreased in the non-IVF group (standardized incidence ratio, 0.58; 95% CI, 0.36-0.88). Women in the IVF group had a significant increase in risk compared with women in the non-IVF group (multivariable-adjusted hazard ratio, 1.80; 95% CI, 1.10-2.94). No trend emerged with more IVF cycles or more ampules of gonadotropins administered. Colorectal cancer risk did not increase with longer follow-up periods. CONCLUSIONS: Although women who receive ovarian stimulation for IVF do not have an increased risk for colorectal cancer compared with the general population, findings from our nationwide cohort study indicate that their risk is increased compared with women who received subfertility treatments other than IVF. Further research is warranted to examine whether ovarian stimulation for IVF contributes to development of colorectal cancer.

Ovarian Stimulation for In Vitro Fertilization and Long-term Risk of Breast Cancer.

IMPORTANCE: Previous studies of breast cancer risk after in vitro fertilization (IVF) treatment were inconclusive due to limited follow-up. OBJECTIVE: To assess long-term risk of breast cancer after ovarian stimulation for IVF. DESIGN, SETTING, AND PARTICIPANTS: Historical cohort (OMEGA study) with complete follow-up through December 2013 for 96% of the cohort. The cohort included 19,158 women who started IVF treatment between 1983 and 1995 (IVF group) and 5950 women starting other fertility treatments between 1980 and 1995 (non-IVF group) from all 12 IVF clinics in the Netherlands. The median age at end of follow-up was 53.8 years for the IVF group and 55.3 years for the non-IVF group. EXPOSURES: Information on ovarian stimulation for IVF, other fertility treatments, and potential confounders was collected from medical records and through mailed questionnaires. MAIN OUTCOMES AND MEASURES: Incidence of invasive and in situ breast cancers in women who underwent fertility treatments was obtained through linkage with the Netherlands Cancer Registry (1989-2013). Breast cancer risk in the IVF group was compared with risks in the general population (standardized incidence ratios [SIRs]) and the non-IVF group (hazard ratios [HRs]). RESULTS: Among 25,108 women (mean age at baseline, 32.8 years; mean number of IVF cycles, 3.6), 839 cases of invasive breast cancer and 109 cases of in situ breast cancer occurred after a median follow-up of 21.1 years. Breast cancer risk in IVF-treated women was not significantly different from that in the general population (SIR, 1.01 [95% CI, 0.93-1.09]) and from the risk in the non-IVF group (HR, 1.01 [95% CI, 0.86-1.19]). The cumulative incidences of breast cancer at age 55 were 3.0% for the IVF group and 2.9% for the non-IVF group (P = .85). The SIR did not increase with longer time since treatment (≥20 years) in the IVF group (0.92 [95% CI, 0.73-1.15]) or in the non-IVF group (1.03 [95% CI, 0.82-1.29]). Risk was significantly lower for those who underwent 7 or more IVF cycles (HR, 0.55 [95% CI, 0.39-0.77]) vs 1 to 2 IVF cycles and after poor response to the first IVF cycle (HR, 0.77 [95% CI, 0.61-0.96] for <4 vs ≥4 collected oocytes). CONCLUSIONS AND RELEVANCE: Among women undergoing fertility treatment in the Netherlands between 1980 and 1995, IVF treatment compared with non-IVF treatment was not associated with increased risk of breast cancer after a median follow-up of 21 years. Breast cancer risk among IVF-treated women was also not significantly different from that in the general population. These findings are consistent with absence of a significant increase in long-term risk of breast cancer among IVF-treated women.

A mouse model for endometrioid ovarian cancer arising from the distal oviduct.

Ovarian cancer is the deadliest gynecological malignancy in Western countries. Early detection, however, is hampered by the fact that the origin of ovarian cancer remains unclear. Knowing that in a high percentage of endometrioid ovarian cancers Wnt/ß-catenin signaling is activated, and in view of the hypothesis that ovarian cancer may originate from the distal oviduct, we studied mice in which Wnt/ß-catenin signaling was activated in Müllerian duct-derived tissues. Conditional adenomatous polyposis coli (Apc) knockout mice were used to study the activation of Wnt/ß-catenin signaling in Müllerian duct-derived organs. These Pgr(Cre/+);Apc(ex15lox/lox) mice (n = 44) were sacrificed at 10, 20, 40 and 80 weeks and uterus, oviduct, ovaries and surrounding fat tissues were assessed using immunohistochemistry. Using nuclear ß-catenin staining, Wnt/ß-catenin signaling activation was confirmed in the entire epithelium of the adult Müllerian duct (fimbriae, oviduct and endometrium), but was absent in ovarian surface epithelium cells (OSEs). Besides endometrial hyperplasia, in 87.2% of mice intraepithelial lesions of the distal oviduct were found, whereas OSEs remained unaffected. In addition, 62.5% of mice developed tumors in the distal and fimbrial part of the oviduct. In the ovaries, mainly at young age, in 16.3% of mice, simple epithelial cysts were noted, which developed further into endometrioid ovarian tumors, resembling human endometrioid ovarian cancer (27.9% of mice). Next to this, locoregional growth in the utero-ovarian ligament was also shown. Here, for the first time, mutations (activation of Wnt/ß-catenin) in the distal oviduct result in precursor lesions that develop into ovarian tumors, resembling human endometrioid ovarian cancer.

Pelvic floor dysfunction: women's sexual concerns unraveled.

INTRODUCTION: Sexual function of women suffering from pelvic organ prolapse (POP) and/or urinary incontinence (UI) is adversely affected. However, our current understanding of the exact relationship between female sexual dysfunction and POP and/or UI is incomplete. A qualitative study can improve our understanding by describing what women themselves perceive as the real problem. AIM: To gain a more in-depth understanding of the impact of POP and/or UI on the different categories of female sexual dysfunction by way of a qualitative study. METHODS: Qualitative semistructured interviews were conducted in 37 women scheduled for pelvic floor surgery, and one was excluded from analysis due to incomplete recordings. MAIN OUTCOME MEASURES: The impact of POP and/or UI on female sexual function. RESULTS: Only 17% of women were completely positive about their sex life. Both POP and UI had a negative effect on body image. Women with POP had a negative image of their vagina, which caused them to be insecure about their partner's sexual experience, while women with UI were embarrassed about their incontinence and pad use, and feared smelling of urine. Worries about the presence of POP during sexual activity, discomfort from POP, and reduced genital sensations were the most important reasons for decreased desire, arousal, and difficulty reaching an orgasm in women with POP. Fear of incontinence during intercourse affected desire, arousal, and orgasm and could be a cause for dyspareunia in women with UI. Desire was divided into two main elements: "drive" and "motivation." Although "drive," i.e., spontaneous sexual interest, was not commonly affected by POP and/or UI, a decrease in "motivation" or the willingness to engage in sexual activity was the most common sexual dysfunction mentioned. CONCLUSIONS: Body image plays a key role in the sexual functioning of women with POP and/or UI with the biggest impact on women's "motivation."

Alterations in Wnt-ß-catenin and Pten signalling play distinct roles in endometrial cancer initiation and progression.

Endometrioid endometrial cancer arises through a gradual series of histological changes, each accompanied by specific alterations in gene expression and activity. Activation of the Wnt-ß-catenin pathway and loss of PTEN activity are frequently observed in endometrial cancers. However, the specific roles played by alterations in these pathways in the initiation and progression of endometrial cancer are currently unclear. Here, we investigated the effects of loss of Pten and Apc gene function in the mouse endometrium by employing tissue-specific and inducible mutant alleles, followed by immunohistochemical (IHC) and loss of heterozygosity (LOH) analysis of their corresponding cancerous lesions. Loss of the Apc function in the endometrium leads to cytoplasmic and nuclear ß-catenin accumulation in association with uterine hyperplasia and squamous cell metaplasia, but without malignant transformation. Loss of Pten function also resulted in squamous metaplasia but, in contrast to loss of Apc function, it initiates endometrial cancer. On the other hand, loss of Apc function in the endometrium accelerates Pten-driven endometrial tumourigenesis. Analysis of compound heterozygous mice confirmed that somatic loss of the wild-type Pten allele represents the rate-limiting initiation step in endometrial cancer. Simultaneous loss of Pten and Apc resulted in endometrial cancer characterized by earlier onset and a more aggressive malignant behaviour. These observations are indicative of the synergistic action between the Wnt-ß-catenin and Pten signalling pathways in endometrial cancer onset and progression.

The risk of primary and contralateral breast cancer after ovarian cancer in BRCA1/BRCA2 mutation carriers: Implications for counseling.

BACKGROUND: The objective of this study was to assess the incidence of primary breast cancer (PBC) and contralateral breast cancer (CBC) in patients who had BRCA1/BRCA2-associated epithelial ovarian cancer (OC). METHODS: From the database of the Rotterdam Family Cancer Clinic, patients who had BRCA-associated OC without a history of unilateral breast cancer (BC) (at risk of PBC; n = 79) or with a history of unilateral BC (at risk of CBC; n = 37) were selected. The control groups consisted of unaffected BRCA mutation carriers (n = 351) or mutation carriers who had a previous unilateral BC (n = 294), respectively. The risks of PBC and CBC were calculated using the Kaplan-Meier survival method with death considered as a competing risk event. RESULTS: Women with BRCA-associated OC had lower 2-year, 5-year, and 10-year risks of PBC (3%, 6%, and 11%, respectively) compared with unaffected mutation carriers (6%, 16%, and 28%, respectively; P = .03), although they had a considerably higher mortality rate at similar time points (13%, 33%, and 61%, respectively, vs 1%, 2%, and 2%, respectively; P < .001). In BRCA mutation carriers with a previous unilateral BC, the 2-year, 5-year, and 10-year risks of CBC were nonsignificantly lower in patients with OC than in those without OC (0%, 7%, and 7%, respectively, vs 6%, 16%, and 34%, respectively; P = .06), whereas the mortality rate was higher in patients with OC (19%, 34%, and 55%, respectively, vs 4%, 11%, and 21%, respectively; P < .001). CONCLUSIONS: Patients with BRCA-associated OC had a lower risk of developing a subsequent PBC or CBC than mutation carriers without OC, whereas the risk of dying from OC was greater than the risk of developing BC. These data may facilitate more tailored counseling for this patient subgroup, although confirmative studies are warranted.

Cancer risk in children, adolescents, and young adults conceived by ART in 1983-2011.

STUDY QUESTION: Do children, adolescents, and young adults born after ART, including IVF, ICSI and frozen-thawed embryo transfer (FET), have an increased risk of cancer compared with children born to subfertile couples not conceived by ART and children from the general population? SUMMARY ANSWER: After a median follow-up of 18 years, the overall cancer risk was not increased in children conceived by ART, but a slight risk increase was observed in children conceived after ICSI. WHAT IS KNOWN ALREADY: There is growing evidence that ART procedures could perturb epigenetic processes during the pre-implantation period and influence long-term health. Recent studies showed (non-)significantly increased cancer risks after ICSI and FET, but not after IVF. STUDY DESIGN SIZE DURATION: A nationwide historical cohort study with prospective follow-up was carried out, including all live-born offspring from women treated with ART between 1983 and 2011 and subfertile women not treated with ART in one of the 13 Dutch IVF clinics and two fertility centers. PARTICIPANTS/MATERIALS SETTING METHODS: Children were identified through the mothers' records in the Personal Records Database. Information on the conception method of each child was collected through the mother's medical record. In total, the cohort comprises 89 249 live-born children of subfertile couples, of whom 51 417 were conceived using ART and 37 832 were not (i.e. conceived naturally, through ovulation induction, or after IUI). Cancer incidence was ascertained through linkage with the Netherlands Cancer Registry for the period 1989-2019. Cancer risk in children conceived using ART was compared with risk in children born to subfertile couples but not conceived by ART (hazard ratio (HR)) and children from the general population (standardized incidence ratios (SIRs)). MAIN RESULTS AND THE ROLE OF CHANCE: In total, 358 cancers were observed after a median follow-up of 18 years. Overall cancer risk was not increased in children conceived using ART, when compared with the general population (SIR = 0.96, 95% CI = 0.81-1.12) or with children from subfertile couples not conceived by ART (HR = 1.06, 95% CI = 0.84-1.33). Compared with children from subfertile couples not conceived by ART, the use of IVF or FET was not associated with increased cancer risk, but ICSI was associated with a slight risk increase (HR = 1.58, 95% CI = 1.08-2.31). Risk of cancer after ART did not increase at older ages (≥18 years, HR = 1.26, 95% CI = 0.88-1.81) compared to cancer risk in children not conceived by ART. LIMITATIONS REASONS FOR CAUTION: The observed increased risk among children conceived using ICSI must be interpreted with caution owing to the small number of cases. WIDER IMPLICATIONS OF THE FINDINGS: After a median follow-up of 18 years, children conceived using ART do not have an increased overall cancer risk. Many large studies with prolonged follow-up are needed to investigate cancer risk in (young) adults conceived by different types of ART. In addition, international pooling of studies is recommended to provide sufficient power to study risk of specific cancer sites after ART. STUDY FUNDING/COMPETING INTERESTS: This work was supported by The Dutch Cancer Society (NKI 2006-3631) that funded the OMEGA-women's cohort, Children Cancer Free (KIKA; 147) that funded the OMEGA-I-II offspring cohort. The OMEGA-III offspring cohort was supported by a Postdoc Stipend of Amsterdam Reproduction & Development, and the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under Award Number R01HD088393. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

The prevalence and risk factors of overactive bladder symptoms and its relation to pelvic organ prolapse symptoms in a general female population.

INTRODUCTION AND HYPOTHESIS: To study the prevalence and risk factors of overactive bladder (OAB) symptoms and its relationship with symptoms of pelvic organ prolapse (POP). METHODS: This is a cross-sectional study including women aged between 45 and 85 years, registered in eight general practices. All women were asked to self complete the validated Dutch translated questionnaires. All symptoms were dichotomized as present or absent based on responses to each symptom and degree of bother. RESULTS: Forty-seven percent of the women filled out the questionnaire. Prevalence of urgency was 34% and the prevalence of any OAB symptoms 49%. Prevalence of OAB symptoms increased with advancing age. Symptoms of POP were an independent risk factor for symptomatic OAB. Other risk factors were continence and prolapse surgery in the past, age above 75, overweight, postmenopausal status and smoking. CONCLUSIONS: The prevalence of any OAB symptoms was 49%. POP symptoms were an independent risk factor for symptomatic OAB.

The effect of hormone therapy on breast density following risk-reducing salpingo-oophorectomy in women with an increased risk for breast and ovarian cancer.

OBJECTIVE: To compare the effect of tibolone to conjugated estrogens with medroxyprogesterone-acetate (CEE + MPA) on breast density, as a predictor for breast cancer risk, in women with a high risk of breast and ovarian cancer. METHODS: Women aged 30-50 (N = 114) who had undergone risk-reducing salpingo-oophorectomy (RRSO) were randomized to tibolone or CEE + MPA. RESULTS: Breast density decreased 46% after RRSO in untreated women, 39% after treatment with tibolone, and 17% after treatment with CEE + MPA; the decrease in breast density after CEE + MPA was significantly different compared with that of untreated women (P = 0.017). CONCLUSIONS: A decline in breast density is seen after premenopausal RRSO despite the use of both CEE + MPA or tibolone, although lower breast density is seen after tibolone use.

Long-Term Risk of Ovarian Cancer and Borderline Tumors After Assisted Reproductive Technology.

BACKGROUND: Long-term effects of assisted reproductive technology (ART) on ovarian tumor risk are unknown. METHODS: This nationwide cohort study comprises 30 625 women who received ovarian stimulation for ART in 1983-2000 and 9988 subfertile women not treated with ART. Incident invasive and borderline ovarian tumors were ascertained through linkage with the Netherlands Cancer Registry and the Dutch Pathology Registry until July 2018. Ovarian tumor risk in ART-treated women was compared with risks in the general population and the subfertile non-ART group. Statistical tests were 2-sided. RESULTS: After a median follow-up of 24 years, 158 invasive and 100 borderline ovarian tumors were observed. Ovarian cancer risk in the ART group was increased compared with the general population (standardized incidence ratio [SIR] = 1.43, 95% confidence interval [CI] = 1.18 to 1.71) but not when compared with the non-ART group (age- and parity-adjusted hazard ratio [HR] = 1.02, 95% CI = 0.70 to 1.50). Risk decreased with higher parity and with a larger number of successful ART cycles (resulting in childbirth, Ptrend = .001) but was not associated with the number of unsuccessful ART cycles. Borderline ovarian tumor risk was increased in ART-treated women compared with the general population (SIR = 2.20, 95% CI = 1.66 to 2.86) and with non-ART women (HR = 1.84, 95% CI = 1.08 to 3.14). Risk did not increase with more ART cycles or longer follow-up time. CONCLUSIONS: Increased ovarian cancer risk in ART-treated women compared with the general population is likely explained by nulliparity rather than ART treatment. The increased risk of borderline ovarian tumors after ART must be interpreted with caution because no dose-response relationship was observed.

Miscarriage risk for IVF pregnancies in poor responders to ovarian hyperstimulation.

The increasing miscarriage rate with advancing female age is attributed to a decline in oocyte quality. A poor response to ovarian hyperstimulation is often an expression of a decrease in oocyte quantity. Although oocyte quality and quantity both decrease as a result of ovarian ageing, it is unclear whether these two processes are related to each other. To investigate the relationship between oocyte quantity and quality, we compared miscarriage rates between IVF treated women with a poor and normal response, respectively. Data were studied from a retrospective nationwide cohort of Dutch women undergoing IVF treatment from 1983 to 1995. Women achieving an ongoing pregnancy after their first complete IVF cycle (n=1468) were compared with those experiencing miscarriage (n=357) with respect to their ovarian response. Logistic regression analysis showed a statistically significant association between poor response (fewer than four retrieved oocytes) and miscarriage (P=0.001). Due to interaction, this association became stronger with increasing female age. Among women < 36 years, miscarriage rates between poor and normal responders did not differ, whereas among women 36 years poor responders had a statistically significant increased miscarriage rate compared with normal responders (P=0.001). These results support the hypothesis of a relationship between quantitative ovarian reserve and oocyte quality.

Prevalence of double incontinence, risks and influence on quality of life in a general female population.

BACKGROUND: Urinary incontinence (UI) and anal incontinence (AI) are complaints with impact on quality of life (QOL). Few data are available on prevalence of double incontinence (DI) in the general female population. OBJECTIVE: To determine prevalence of UI, AI, and DI, their associations with age, parity, and effects on QOL. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study on a general female population, aged 45-85 years. MEASUREMENTS: Validated questionnaires measuring pelvic floor dysfunction and QOL. A short questionnaire was used for non-responders. Analyses were performed with Chi-square tests, ANOVA, and logistic regression. RESULTS: Response rate was 62.7% (1,869/2,979); 59% of non-responders filled in the short questionnaire (620/1,051). No significant differences in stress urinary incontinence, vaginal bulging, solid stool incontinence and parity were found between responders and non-responders. DI with and without flatal incontinence were reported by 7.7% and 35.4%, respectively. Women with urge urinary incontinence (UUI) alone had an OR of 4.3 (95% CI 2.4-7.9) for liquid stool incontinence, 1.6 (95% CI 0.5-4.9) for solid stool incontinence and 2.4 for flatal incontinence (95% CI 1.5-3.8). Women with AI had an OR of 5.8 (95% CI 1.8-18.2) for UUI. Women with DI including flatus reported significantly poorer QOL. Limitation of the study was the lack of objective clinical validation of symptoms, which may have influenced the real prevalence data. CONCLUSIONS: Most important relation was found between UUI and liquid stool incontinence (OR 4.3). We recommend that clinicians take the history of patients with UUI or mixed urinary incontinence to exclude the co-existence of AI.

Recurrence rate in vulvar carcinoma in relation to pathological margin distance.

OBJECTIVES: This paper describes the results of a retrospective study of surgical approaches and recurrence rates relating to patients with squamous cell carcinoma (SCC) of the vulva. The aim of this study was to analyze the histological margins in relation to recurrence rate and survival. METHODS: A retrospective chart review of 93 cases of vulvar cancer. The data collected included clinicopathological and surgical characteristics and the following potential risk factors: pathological margin distance, less than 8 mm; stromal invasion depth, more than 2.5 mm; tumor size; and presence of benign or premalignant epithelial disorders. RESULTS: Ninety-three patients (median age, 74 years) underwent modified radical vulvectomy, hemi-vulvectomy, or local wide excision for SCC of the vulva from 2000 to 2005. The tumor was radically removed in 80 patients (86%), although the histopathological margin was less than 8 mm in 50 patients (54%). Eighteen patients (23%) developed a local recurrence. The recurrence rate did not differ between patients in whom the margin distance was 8 mm or more and those in whom the margin distance was less than 8 mm, (23% and 22%, respectively). The median follow-up was 31 months (range, 2-90 months). CONCLUSIONS: Several studies showed that pathological margin distance of more than 8 mm is an important predictor for local recurrence. This finding was not confirmed in the present study.