Christian Ottosen

Two successful pregnancies following autotransplantation of frozen/thawed ovarian tissue

BACKGROUND Cryopreservation of the ovarian cortex with subsequent autotransplantation has, on an experimental basis, been performed to preserve fertility in women being treated for a malignant disease. The present study reports ovarian activity and pregnancies following autotransplantation of frozen/thawed ovarian tissue. METHODS One complete ovary was cryopreserved from each of six patients who were 26-35 years old prior to treatment. Tissue from three of the patients was transported 4-5 h on ice prior to cryopreservation. After a period of 17-32 months, orthotopic autotransplantation was performed replacing 20-60% of the tissue. Two patients received additional heterotopic transplants. RESULTS In all cases, the tissue restored menstrual cyclicity 14-20 weeks following transplantation. Four of the six women conceived following assisted reproduction: two women (who had the tissue transported 4-5 h prior to cryopreservation) each, based on the orthotopic transplanted tissue, delivered one healthy child (February 2007 and January 2008); one woman miscarriaged in gestational Week 7; and the other had a positive hCG test but no clinical pregnancy. The remaining two women did not become pregnant. CONCLUSIONS Two additional healthy children have been born as a result of the ovarian cryopreservation procedure. In both cases, the ovarian tissue was transported 4-5 h prior to freezing demonstrating that hospitals may offer cryopreservation without having the necessary expertise locally.

Effect of virtual reality training on laparoscopic surgery: randomised controlled trial

Objective To assess the effect of virtual reality training on an actual laparoscopic operation. Design Prospective randomised controlled and blinded trial. Setting Seven gynaecological departments in the Zeeland region of Denmark. Participants 24 first and second year registrars specialising in gynaecology and obstetrics. Interventions Proficiency based virtual reality simulator training in laparoscopic salpingectomy and standard clinical education (controls). Main outcome measure The main outcome measure was technical performance assessed by two independent observers blinded to trainee and training status using a previously validated general and task specific rating scale. The secondary outcome measure was operation time in minutes. Results The simulator trained group (n=11) reached a median total score of 33 points (interquartile range 32-36 points), equivalent to the experience gained after 20-50 laparoscopic procedures, whereas the control group (n=10) reached a median total score of 23 (22-27) points, equivalent to the experience gained from fewer than five procedures (P<0.001). The median total operation time in the simulator trained group was 12 minutes (interquartile range 10-14 minutes) and in the control group was 24 (20-29) minutes (P<0.001). The observers’ inter-rater agreement was 0.79. Conclusion Skills in laparoscopic surgery can be increased in a clinically relevant manner using proficiency based virtual reality simulator training. The performance level of novices was increased to that of intermediately experienced laparoscopists and operation time was halved. Simulator training should be considered before trainees carry out laparoscopic procedures. Trial registration ClinicalTrials.gov NCT00311792.

Autotransplantation of cryopreserved ovarian tissue in 12 women with chemotherapy-induced premature ovarian failure: the Danish experience

OBJECTIVE To describe a cohort of 12 Danish women who received autotransplantation of frozen-thawed cryopreserved ovarian tissue because of premature ovarian failure after cancer treatment. DESIGN Retrospective study. SETTING University hospitals. PATIENT(S) Twelve women with autotransplanted frozen-thawed ovarian tissue. INTERVENTION(S) Monitoring of hormonal parameters and results of 56 IVF cycles in 10 women. MAIN OUTCOME MEASURE(S) Levels of gonadotropins and sex steroids, functional life span of the grafts, and results of IVF. RESULT(S) All 12 women regained ovarian function between 8 and 26 weeks (mean 19 weeks) after transplantation. Ten women underwent a total of 56 IVF cycles, 76 follicles developed, 49 oocytes were aspirated, 18 were fertilized, and 16 embryos were transferred resulting in six pregnancies: two biochemical, one clinical that miscarried in week 7, and two ongoing resulting in the delivery of two healthy infants born at term to two women. One of these women subsequently conceived spontaneously and delivered another healthy infant. The life span of the transplanted tissue has been between 6 months and still functioning after 54 months. CONCLUSION(S) Autotransplantation consistently leads to recovery of ovarian function after treatment-induced ovarian failure. Four women became pregnant, after IVF or spontaneously, resulting in the delivery of three healthy infants.

Objective assessment of surgical competence in gynaecological laparoscopy: development and validation of a procedure‐specific rating scale

Objective  The purpose of this study was to develop a global‐ and a procedure‐specific rating scale based on a well‐validated generic model (objective structured assessment of technical skills) for assessment of technical skills in laparoscopic gynaecology. Furthermore, we aimed to investigate the construct validity and the interrater agreement (IRA) of the rating scale. We investigated both the gamma coefficient (Kendall’s rank correlation), which is a measure of the strength of dependence between observations, and the kappa value for each of the ten individual items included in the rating scale.

The effect of accelerated rehabilitation on recovery after surgery for ovarian malignancy

Background. In patients undergoing colonic surgery the postoperative hospital stay has been reduced from 8–12 days to 2–4 days with multimodal rehabilitation programs. The aim of this study was to evaluate the postoperative outcome after surgery for ovarian malignancy with conventional care compared to fast‐track multimodal rehabilitation. Methods. Seventy‐two consecutive patients receiving conventional care (group 1) were compared with 69 consecutive patients receiving multimodal, fast‐track rehabilitation with a planned care program including continuous epidural analgesia, early oral feeding and mobilization (group 2) in the same department. Outcome was postoperative hospital stay and morbidity during the first postoperative month. Results. Median age was 63 years (group 1) and 62 years (group 2). Median postoperative hospital stay was reduced from 6 days in group 1 (mean 7.3) to 5 days in group 2 (mean 5.4) (p<0.05). There was no difference in the overall complication rate, although severe medical complications were reduced in group 2 (14% versus 2%; p<0.01). Readmission rate was 10% in group 1 and 3% in group 2 (p>0.05). Conclusions. The concept of fast‐track multimodal rehabilitation appears to be beneficial in patients operated for ovarian malignancy, as hospital stay and medical morbidity are reduced.

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.

Organisation and quality of primary surgical intervention for ovarian cancer in Denmark

Background. The positive effect on survival of maximal primary cytoreductive surgery for ovarian cancer is well established, and the highest rates of optimal cytoreduction are achieved by gynecological oncologists. Danish women have not only one of the highest incidences of ovarian cancer, but also the highest mortality rate. From 1981 to 1989, the overall Danish optimal debulking rate was 25% in patients with stage III and IV tumors. The primary aim of the present study was, therefore, to evaluate the organisation and quality of current primary surgical intervention for ovarian cancer in Denmark. Methods. All women diagnosed with epithelial ovarian carcinoma (DC56) were identified through the Danish National Patient Registry during the study period from 1 July 2002 to 31 December 2003, and surgical notes and histopathology were evaluated by a board of 7 gynecological‐oncologists, focusing on maximal cytoreduction. Results. For stage III, the nationwide optimal debulking rate was 39%, significantly higher in the major hospitals (49%) versus other hospitals (29%) (p<0.005). In 19% of cases, there was insufficient information to evaluate debulking from the surgical notes, significantly less at the major hospitals versus other hospitals (12 versus 25%, p<0.001). Conclusions. In Denmark, the quality of the primary surgical intervention for ovarian cancer is not optimal. In order to enhance survival, compliance with international guidelines and improved registration of the surgical procedures in clinical databases are mandatory.

An open prospective randomized study of dinoproston and gemeprost in second trimester legal abortions

The aim of this open prospective randomized study was to compare two non‐invasive methods for second trimester abortion using gemeprost pessaries (Cervagem®) and dinoproston gel (Cerviprost®) concerning effectiveness, time for abortion, consumption of analgesics, infection‐rate and side‐effects.