Berit Jul Mosgaard

Infertility, fertility drugs, and invasive ovarian cancer : a case-control study

OBJECTIVE To assess the risk of invasive ovarian cancer among infertile women treated with fertility drugs. DESIGN A case-control study. SETTING Nationwide data based on public registers. PATIENT(S) All Danish women (below the age of 60 years) with ovarian cancer during the period from 1989 to 1994 and twice the number of age-matched population controls. Included in the analysis were 684 cases and 1,721 controls. MAIN OUTCOME MEASURE(S) Influence of parity, infertility, and fertility drugs on the risk of ovarian cancer after multivariate confounder control. Risk measure(s): odds ratios (OR) with 95% confidence intervals. RESULT(S) Nulliparous women had an increased risk of ovarian cancer compared with parous women: OR 1.5 to 2.0. Infertile, nontreated nulliparous women had an OR of 2.7 (1.3 to 5.5) compared with noninfertile nulliparous women. The OR of ovarian cancer among treated nulliparous women was 0.8 (0.4 to 2.0) and among treated parous 0.6 (0.2 to 1.3), compared with nontreated nulliparous and parous infertile women, respectively. CONCLUSION(S) Nulliparity implies a 1.5- to 2-fold increased risk of ovarian cancer. Infertility without medical treatment among these women increased the risk further. Among parous as well as nulliparous women, treatment with fertility drugs did not increase the ovarian cancer risk compared with nontreated infertile women.

Stage at diagnosis and ovarian cancer survival: evidence from the International Cancer Benchmarking Partnership.

OBJECTIVE We investigate what role stage at diagnosis bears in international differences in ovarian cancer survival. METHODS Data from population-based cancer registries in Australia, Canada, Denmark, Norway, and the UK were analysed for 20,073 women diagnosed with ovarian cancer during 2004-07. We compare the stage distribution between countries and estimate stage-specific one-year net survival and the excess hazard up to 18 months after diagnosis, using flexible parametric models on the log cumulative excess hazard scale. RESULTS One-year survival was 69% in the UK, 72% in Denmark and 74-75% elsewhere. In Denmark, 74% of patients were diagnosed with FIGO stages III-IV disease, compared to 60-70% elsewhere. International differences in survival were evident at each stage of disease; women in the UK had lower survival than in the other four countries for patients with FIGO stages III-IV disease (61.4% vs. 65.8-74.4%). International differences were widest for older women and for those with advanced stage or with no stage data. CONCLUSION Differences in stage at diagnosis partly explain international variation in ovarian cancer survival, and a more adverse stage distribution contributes to comparatively low survival in Denmark. This could arise because of differences in tumour biology, staging procedures or diagnostic delay. Differences in survival also exist within each stage, as illustrated by lower survival for advanced disease in the UK, suggesting unequal access to optimal treatment. Population-based data on cancer survival by stage are vital for cancer surveillance, and global consensus is needed to make stage data in cancer registries more consistent.

Ovarian stimulation and borderline ovarian tumors: a case-control study

OBJECTIVE To assess the risk of borderline ovarian cancer among infertile women treated with fertility drugs. DESIGN Case-control study. SETTING Nationwide data obtained from public registers and postal questionnaires. PATIENT(S) All Danish women <60 years old with borderline ovarian cancer during the period 1989-1994 and randomly selected population controls. The analysis included 231 cases and 1,721 controls. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Influence of parity, infertility, and fertility drugs on the risk of borderline ovarian cancer after multivariate confounder control. RESULT(S) The odds ratio (OR) for borderline ovarian cancer among infertile untreated nulliparous women compared with fertile nulliparous women was 1.9. The OR for borderline ovarian cancer among treated nulliparous women compared with untreated infertile nulliparous women was 1.5, and the OR among treated parous women compared with untreated infertile parous women was 1.5. CONCLUSION(S) Among fertile women, the difference in the risk of borderline ovarian cancer between nulliparous women and parous women was not statistically significant. Nulliparous women who were infertile and who did not receive medical treatment had a twofold higher risk of borderline ovarian cancer than fertile nulliparous women. There was no statistically significant increase in the risk of borderline ovarian cancer among nulliparous women who were treated with fertility drugs compared with nulliparous untreated infertile women or among parous women who were treated with fertility drugs compared with parous untreated infertile women.

The impact of parity, infertility and treatment with fertility drugs on the risk of ovarian cancer: A survey

The etiology of ovarian cancer is multifactorial. With our present knowledge, etiological factors are only found in a minority of cases. In the industrialized world, 10 new cases of ovarian cancer are developed per 100,000 women per year (1). Women who experience one or more deliveries have a reduced risk of ovarian cancer compared with nulliparous women (2-7). There is a dose-response relationship so that the risk of ovarian cancer is diminished every time a woman gives birth. It is not finally established whether the increased risk of ovarian cancer among infertile women is due to the relative high proportion of nulliparous women among these women, or whether it is due to some kind of ovarian pathology, which may be responsible for the infertility as well as for the increased risk of ovarian cancer. One of the difficulties in assessing the significance of infertility for ovarian cancer is the close connection between parity and fertility and between nulliparity and infertility (8). Furthermore, an epidemiological analysis of these problems has to face the fact that these ‘spontaneous conditions’ are influenced by, for example, the treatment with

Does neoadjuvant chemotherapy impair long-term survival for ovarian cancer patients? A nationwide Danish study

OBJECTIVE In Denmark, the proportion of women with ovarian cancer treated with neoadjuvant chemotherapy (NACT) has increased, and the use of NACT varies among center hospitals. We aimed to evaluate the impact of first-line treatment on surgical outcome and median overall survival (MOS). METHODS All patients treated in Danish referral centers with stage IIIC or IV epithelial ovarian cancer from January 2005 to October 2011 were included. Data were obtained from the Danish Gynecological Cancer Database, the Danish National Patient Register and medical records. RESULTS Of the 1677 eligible patients, 990 (59%) were treated with primary debulking surgery (PDS), 515 (31%) with NACT, and 172 (10%) received palliative treatment. Of the patients referred to NACT, 335 (65%) received interval debulking surgery (IDS). Patients treated with NACT-IDS had shorter operation times, less blood loss, less extensive surgery, fewer intraoperative complications and a lower frequency of residual tumor (p < 0.05 for all). No difference in MOS was found between patients treated with PDS (31.9 months) and patients treated with NACT-IDS (29.4 months), p = 0.099. Patients without residual tumor after surgery had better MOS when treated with PDS compared with NACT-IDS (55.5 and 36.7 months, respectively, p = 0.002). In a multivariate analysis, NACT-IDS was associated with increased risk of death after two years of follow-up (HR: 1.81; CI: 1.39-2.35). CONCLUSIONS No difference in MOS was observed between PDS and NACT-IDS. However, patients without residual tumor had superior MOS when treated with PDS, and NACT-IDS could be associated with increased risk of death after two years of follow-up.

Sexual Functioning and Vaginal Changes after Radical Vaginal Trachelectomy in Early Stage Cervical Cancer Patients: A Longitudinal Study

INTRODUCTION Radical vaginal trachelectomy (RVT) offers low complication rate, good survival, and possibility for future childbearing for young women with early stage cervical cancer. However, the literature on quality of life (QOL) and sexual functioning in patients undergoing RVT is scarce. AIM The aims of this study were to prospectively assess sexual function after RVT and to compare scores of sexual function in patients operated by RVT and radical abdominal hysterectomy (RAH) with those of age-matched control women from the general population. METHODS Eighteen patients with early stage cervical cancer operated with RVT were prospectively included and assessed preoperatively, and 3, 6, and 12 months postoperatively using validated questionnaires. RAH patients were included consecutively and assessed once at 12 months postsurgery, while an age-matched control group of 30 healthy women was assessed once. MAIN OUTCOME MEASURE Sexual dysfunction total score as measured by the Female Sexual Function Index (FSFI) was the main outcome measure. RESULTS During the 12 months posttreatment, RVT patients tended to have persistent sexual dysfunction as measured by FSFI (mean overall score <26.55 at each assessment) and Female Sexual Distress Scale (mean overall score > 11). Sexual worry (P < 0.001) and lack of sexual desire (P = 0.038) were more frequently reported among patients in both treatment groups compared with control women. Sexual activity increased significantly during the observation time for the RVT group (P = 0.023) and reached that of healthy women. Global Health Status score improved over time for the RVT group but never reached that of healthy control women (P = 0.029). CONCLUSIONS Our data suggest that patients treated with RVT for early stage cervical cancer experience persistent sexual dysfunction up to one year post surgery influencing negatively on their QOL.

Vaginal Radical Trachelectomy for early stage cervical cancer. Results of the Danish National Single Center Strategy

OBJECTIVE To present and evaluate an unselected national single center strategy with fertility preserving trachelectomy in cervical cancer. In 2003 nationwide single-center referral of women for trachelectomies was agreed upon between all Danish departments performing cervical cancer surgery with the purpose of increasing volume, to increase surgical safety and facilitate follow-up. METHODS Prospective data were recorded in the Danish Gynecological Cancer Database of all Vaginal Radical Trachelectomies (VRT) performed in Denmark between 2002 and 2013. Oncologic, fertility and obstetrical outcomes of 120 unselected consecutive VRTs were assessed. To obtain complete follow-up about fertility treatment, pregnancy and obstetric outcome the women filled out an electronic questionnaire. Median follow-up: 55.7 months. RESULTS 85.8% of the patients had stage IB1 disease, 68.3% squamous cell carcinomas, 30.0% adenocarcinomas and 1.7% adenosquamous carcinomas. Six recurrences (5.1%) and 2 deaths (1.7%) occurred. Four women with adenocarcinomas (10.5%) had recurrences, compared to two women with squamous cell carcinomas (2.5%). Seventy-two women (60.0%) desired to conceive and 55 women obtained a total of 77 pregnancies. Of the 72 women 40 were referred to fertility treatment. First and second trimester miscarriage rates were 21.6% and 2.7%, respectively. A total of 53 children were born of which 41 were delivered after gestational week 34. CONCLUSION This unselected national single center referral study confirms the oncological safety of Vaginal Radical Trachelectomy. The complete follow-up regarding reproductive data, reveals a surprisingly extensive need of fertility treatment and due to the rate of prematurity, these pregnancies must be regarded as high-risk pregnancies.

Use of fertility drugs in Denmark 1973-1993 An analysis based on sale statistics

Objectives. The increasing use of drugs for ovarian stimulation and the possibility of long‐term risks has actualized a quantitative assessment of the use of such therapy. The aim of the study was to analyze the development in the sale of different types of drugs used for ovarian stimulation in Denmark during the last two decades.

Validation of epithelial ovarian cancer and fallopian tube cancer and ovarian borderline tumor data in the Danish Gynecological Cancer Database.

Objective. To validate the data on epithelial ovarian cancer, fallopian tube cancer and borderline ovarian tumors registered in the nationwide Danish Gynecological Cancer Database (DGCD) in 2005 and 2006. The DGCD is a multidisciplinary database that contains data for research and quality improvement. Design. Comparative registry‐based study supplemented with data from medical records. Setting. Six hospitals in Denmark. Participants. Women registered with epithelial ovarian cancer, fallopian tube cancer and borderline ovarian tumor. Main outcome measure. Data completeness and strength of agreement. Results. The estimated completeness of reporting to the DGCD was 94.2% and the strength of agreement between the variables in the DGCD and the medical file varied from moderate to very good. The important quality indicator ‘complication’ had the lowest strength of agreement. Conclusion. The validity of ovarian cancer data in the DGCD is sufficient for quality monitoring in gynecological oncology.

The results of gynecologic surveillance in families with hereditary nonpolyposis colorectal cancer

OBJECTIVE We aimed to estimate the incidence rate of endometrial cancer (EC) and to evaluate the results of EC-surveillance in hereditary nonpolyposis colorectal cancer (HNPCC) families. METHODS All at-risk women recommended for EC-surveillance by the HNPCC-register-2959 women (19,334women years)-were included. Data on EC-surveillance were available for 871 women (6894women years), who had performed 1945 surveillance visits. The average surveillance period was 7.9 (range 0.1-21.7) years and 46% of the women had had less than 3years between their visits. RESULTS During 19,334women years, 60 women with gynecological malignancies or premalignancies were diagnosed. Thirty-nine women had EC. Of these, 31 were from families with identified MMR gene mutations with the median age at diagnosis of 54 (39-83) years (Incidence Rate, IR=0.63 per 100women years) and four women from each Amsterdam (AMS)-positive and AMS-like families (median age 64 (55-73) years, IR=0.06 and 0.05 per 100women years, respectively, p<.0001). Among the 871 surveilled women, 13 EC were found: 7/13 cases were diagnosed by surveillance examination-two as prevalent cancers, diagnosed at the first visit-and 6/13 based on symptoms. In addition, five complex atypical hyperplasias and four ovarian cancers (OCs) were diagnosed. All these women were MMR mutation carriers. CONCLUSION Based on 19,334women years of EC-surveillance, our analysis provides a thorough estimation of the EC risk in women with an MMR mutation, or suspected of having Lynch syndrome. We conclude that EC surveillance should only be targeted at MMR-mutation carriers.