Fertility potential and safety assessment of residual ovarian cortex in young women diagnosed with epithelial borderline and early-stage malignant ovarian tumors.

OBJECTIVE: To establish the safety and quality of ovarian cortex surrounding epithelial ovarian tumors in women eligible for fertility-sparing surgery by identifying occult malignant lesions and characterizing the ovarian follicle pool. METHODS: Multicentric retrospective study of 48 subjects (15-45 years), diagnosed with borderline ovarian tumors (BOTs) or early-stage epithelial ovarian cancers (EOCs) and eligible for fertility-sparing surgery. Histological samples of ovarian cortex surrounding tumors were analyzed to characterize the follicle pool, find any occult malignant lesion using tumor-specific markers (cytokeratin 7 and mucin 1), and quantify tumor-infiltrating lymphocytes (TILs) by CD3 and tumor associated macrophages (TAMs) by CD68. RESULTS: Occult ovarian lesions were observed in 6 out of 45 cases investigated (14.6%), including one mucinous stage-I BOT (1/14), one serous stage-I BOT (1/13), 3 advanced-stage serous BOTs (3/11) and one early-stage serous EOC (1/7). Notably, follicle density was significantly lower in subjects diagnosed with ovarian tumors compared to controls (p < 0.001) and at a younger age. Significantly higher follicle atresia was encountered in the ovarian tumor group then in controls (20.1 ± 8.8% vs 9.2 ± 9.4%, p < 0.001) at all ages. Both TILs and TAMs were found in ovarian tumors irrespective of histotype, but no link was established with the status of the ovarian reserve. CONCLUSIONS: Personalized counseling for fertility preservation is required in the event of BOTs and early-stage EOCs. Fertility-sparing surgery and adjuvant gamete preservation should be considered, balancing the oncological risks according to tumor stage and histotype and fertility potential, especially at a younger age.

Assessment of protein biomarkers for preoperative differential diagnosis between benign and malignant ovarian tumors.

OBJECTIVE: To estimate the diagnostic value of tumor and immune related proteins in the discrimination between benign and malignant adnexal masses, and between different subgroups of tumors. METHODS: In this exploratory diagnostic study, 254 patients with an adnexal mass scheduled for surgery were consecutively enrolled at the University Hospitals Leuven (128 benign, 42 borderline, 22 stage I, 55 stage II-IV, and 7 secondary metastatic tumors). The quantification of 33 serum proteins was done preoperatively, using multiplex high throughput immunoassays (Luminex) and electrochemiluminescence immuno-assay (ECLIA). We calculated univariable areas under the Receiver Operating Characteristic Curves (AUCs). To discriminate malignant from benign tumors, multivariable ridge logistic regression with backward elimination was performed, using bootstrapping to validate the resulting AUCs. RESULTS: CA125 had the highest univariable AUC to discriminate malignant from benign tumors (0.85, 95% confidence interval 0.79-0.89). Combining CA125 with CA72.4 and HE4 increased the AUC to 0.87. For benign vs borderline tumors, CA125 had the highest univariable AUC (0.74). For borderline vs stage I malignancy, no proteins were promising. For stage I vs II-IV malignancy, CA125, HE4, CA72.4, CA15.3 and LAP had univariable AUCs ≥0.80. CONCLUSIONS: The results confirm the dominant role of CA125 for identifying malignancy, and suggest that other markers (HE4, CA72.4, CA15.3 and LAP) may help to distinguish between stage I and stage II-IV malignancies. However, further research is needed, also to investigate the added value over clinical and ultrasound predictors of malignancy, focusing on the differentiation between subtypes of malignancy.

Current status of hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer in the United States.

OBJECTIVES: 1.) To compare frequency of HIPEC use in ovarian cancer treatment before and after publication of the phase III study by van Driel et al. in January 2018. 2.) To compare associated rates of hospital-based outcomes, including length of stay, intensive care unit (ICU) admission, complications, and costs in ovarian cancer surgery with or without HIPEC. METHODS: We queried Vizient's administrative claims database of 550 US hospitals for ovarian cancer surgeries from January 2016-January 2020 using ICD-10 diagnosis and procedure codes. Sodium thiosulfate administration was used to identify HIPEC cases according to the published protocol. Student t-tests and relative risk (RR) were used to compare continuous variables and contingency tables, respectively. RESULTS: 152 ovarian cancer patients had HIPEC at 39 hospitals, and 20,014 ovarian cancer patients had surgery without HIPEC at 256 hospitals. Following the trial publication, 97% of HIPEC cases occurred. During the index admission, HIPEC patients had longer median length of stay (8.4 vs. 5.7 days, p < 0.001) and higher percentage of ICU admissions (63.1% vs. 11.0%, p < 0.001) and complication rates (RR = 1.87, p = 0.002). Index admission direct costs ($21,825 vs. $12,038, p < 0.001) and direct cost index (observed/expected costs) (1.87 vs. 1.11, p < 0.001) were also greater in the HIPEC patients. No inpatient deaths or 30-day readmissions were identified after HIPEC. CONCLUSIONS: Use of HIPEC for ovarian cancer increased in the US after publication of a phase III clinical trial in a high-impact journal, though the absolute number of cases remains modest. Incorporation of HIPEC was associated with increased cost, hospital length of stay, ICU admission, and hospital-acquired complication rates. Further studies are needed in order to evaluate long-term outcomes, including morbidity and survival.

Early Assessment of Response to Neoadjuvant Chemotherapy with 18F-FDG-PET/CT in Patients with Advanced-Stage Ovarian Cancer.

PURPOSE: The aim of this study was to evaluate the ability of sequential 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) after one cycle of neoadjuvant chemotherapy (NAC) to predict chemotherapy response before interval debulking surgery (IDS) in advanced-stage ovarian cancer patients. MATERIALS AND METHODS: Forty consecutive patients underwent 18F-FDG-PET/CT at baseline and after one cycle of NAC. Metabolic responses were assessed by quantitative decrease in the maximum standardized uptake value (SUVmax) with PET/CT. Decreases in SUVmax were compared with cancer antigen 125 (CA-125) level before IDS, response rate by Response Evaluation Criteria in Solid Tumors criteria before IDS, residual tumor at IDS, and I chemotherapy response score (CRS) at IDS. RESULTS: A 40% cut-off for the decrease in SUVmax provided the best performance to predict CRS 3 (compete or near-complete pathologic response), with sensitivity, specificity, and accuracy of 81.8%, 72.4%, and 72.4%, respectively. According to this 40% cut-off, there were 17 (42.5%) metabolic responders (≥ 40%) and 23 (57.5%) metabolic non-responders (< 40%). Metabolic responders had higher rate of CRS 3 (52.9% vs. 8.7%, p=0.003), CA-125 normalization (< 35 U/mL) before IDS (76.5% vs. 39.1%, p=0.019), and no residual tumor at IDS (70.6% vs. 31.8%, p=0.025) compared with metabolic non-responders. There were significant associations with progression-free survival (p=0.021) between metabolic responders and non-responders, but not overall survival (p=0.335). CONCLUSION: Early assessment with 18F-FDG-PET/CT after one cycle of NAC can be useful to predic response to chemotherapy before IDS in patients with advanced-stage ovarian cancer.

Assessment of safety and efficacy of pine bark extract in normal and ovariectomized mice.

We evaluated the influence of pine bark extract (PBE) on organs, the cytochrome-P450 (CYP) activities in liver and estrogenic effects in normal and ovariectomized (OVX) female mice. The PBE did not affect organ weights and liver-function indexes (activities of alkaline phosphatase, aspartate amino transferase, and alanine amino transferase) at doses; 0.04%, 0.4%, and 2.0% PBE in the diet, in normal and OVX female mice. In the OVX mice, CYP1A1 activity was significantly higher in the 0.4% and 2.0% PBE groups than in the OVX control group, and in the 0.4% and 2.0% PBE groups were significantly higher than in the 0.04% PBE group. CYP1A2 and 3A4 activities were significantly higher in the 2.0% PBE group than in all other groups. The PBE did not affect uterine weight and femoral bone mineral density at all PBE doses. These results showed that the dose of PBE at the recommended human intake, had no toxic and estrogenic effects in normal female and OVX mice, however, it may need attention to use the excess intake of PBE with some drugs in postmenopausal women.

Combination of Sonographic Morphology Score and Tumor Markers for Detecting Postoperative Recurrent Pelvic Ovarian Carcinoma: Compared With MRI Assessment.

To assess the efficacy of the combination of sonographic morphology score (SMS) with CA125 and HE4 for detecting recurrent pelvic ovarian carcinoma (OC). Data of 58 OC patients treated in our hospital between 2014 and 2016 were analyzed. After cytoreductive surgery and routine chemotherapy, all patients were followed up by transvaginal ultrasound examination (SMS for pelvic masses based on volume and structure scores) and tumor marker (serum CA125 and HE4) detection. Clinical diagnosis of recurrent OC was based on physical examination, magnetic resonance imaging, and punctured pathology for pelvic masses. Receiver operating characteristic (ROC) curves of SMS and the tumor markers were generated, and areas under the curve (AUC) values were assessed. There were 26 patients with tumor recurrence and 32 cases with no recurrence. Magnetic resonance imaging had 100% sensitivity and specificity. The areas under the ROC curves of SMS, CA125, HE4, and SMS-CA125-HE4 were 0.816, 0.825, 0.737, and 0.903, respectively. There was no significant difference in AUC values between SMS and CA125 or HE4. There were significant differences in AUC values between SMS-CA125-HE4 and SMS (Z = 2.48, P = 0.042), CA125 (Z = 2.38, P = 0.046), and HE4 (Z = 6.48, P = 0.016), respectively. With a cutoff value of SMS, 5; CA125, 35 U/mL; HE4, 105 pmol/L, the sensitivity, specificity, positive prognostic value, and negative prognostic value of SMS-CA125-HE4 for recurrent OC assessment were 0.9231, 0.8438, 0.8276, and 0.931, respectively. SMS-CA125-HE4 was correlated with recurrent OC (χ = 30.7428, P < 0.0001). Ultrasound combined with tumor markers may improve the diagnostic efficiency of recurrent OC.

Fertility preservation in children and adolescents: current options and considerations.

PURPOSE OF REVIEW: The purpose of this review is to outline current pediatric fertility preservation options, and discuss ethical and financial considerations impacting this rapidly expanding field. RECENT FINDINGS: With the improvement in treatment of pediatric malignancies and medical conditions that threaten fertility, survival rates are increasing. Therefore, minimizing long-term morbidities such as gonadal damage and infertility is of utmost importance. Impaired fertility not only has a significant negative impact on patient's quality of life; in women, gonadal damage puts patients at risk for premature menopause, and increased risk of cardiac, skeletal, and cognitive issues. Fortunately, fertility preservation options exist for both female and male prepubertal and pubertal patients, and discussion of such options with patients and their families prior to the initiation of therapy and/or before further deterioration of gonadal function is crucial. A multidisciplinary approach to fertility counseling, with attention to the patient's goals and cultural beliefs, is ideal. SUMMARY: Although several national organizations support integrating a fertility consultation into routine care, fertility preservation is still underutilized. Continued research is needed to understand barriers for patients/families and reduce the number of missed opportunities for fertility preservation.

Adjuvant ovarian suppression for resected breast cancer: 2017 critical assessment.

Currently available data supporting adjuvant ovarian function suppression for resected breast cancer in premenopausal women in addition to standard chemotherapy and tamoxifen are not persuasive, even though an ASCO guideline supports them. Available information from the key trial, called "SOFT," has only 5-year follow-up in a 15-year disease. It employs breast cancer events as an endpoint, rather than distant metastases, or better still, death from any cause. The small advantages reported to date may disappear when aromatase inhibitors are given after the occurrence of menopause in the control population. Caution should be exercised in recommending ovarian suppression in all but the highest-risk situations.

No. 341-Diagnosis and Management of Adnexal Torsion in Children, Adolescents, and Adults.

OBJECTIVE: To review the evidence and provide recommendations on the diagnosis and management of adnexal torsion in children, adolescents, and women. OUTCOMES: Elements evaluated include the risk factors, diagnostic accuracy, management options, and outcomes of adnexal torsion. EVIDENCE: Published literature was retrieved through searches of MEDLINE, Embase, CINAHL, and the Cochrane Library using appropriate controlled vocabulary and key words ("adnexal torsion," "ovarian torsion"). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Searches were updated on a regular basis and new material incorporated in the guideline to December 2014. Grey (unpublished) literature was identified through searching the websites of health technology assessment and related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. VALUES: The evidence obtained was reviewed and evaluated by the Canadian Paediatric and Adolescent Gynaecology and Obstetrics Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) under the leadership of the principal authors. Recommendations were made according to guidelines developed by the Canadian Task Force on the Periodic Health Examination. BENEFITS, HARMS AND COSTS: Guideline implementation should assist the practitioner in developing an optimal approach to the diagnosis and management of adnexal torsion while minimizing harm and improving patient outcomes. VALIDATION: These guidelines have been reviewed and approved by the Gynaecology Committee of the SOGC and approved by the council of the SOGC. SPONSOR: The Society of Obstetricians and Gynaecologists of Canada SUMMARY STATEMENTS: RECOMMENDATIONS.

Assessment of ovarian reserve in patients with ovarian endometriosis following laparoscopic enucleation of a cyst accompanied by CO2 laser ablation or electroablation.

INTRODUCTION: Endometriosis affects about 5-15% of women in the reproductive period. One of the most important complications of pelvic endometriosis is infertility. OBJECTIVE: The assessment of ovarian endometriosis therapy with the use of combined laparoscopic techniques (cyst enucleation with electroablation/CO2 laser ablation) and their influence on the preservation of the ovarian reserve. MATERIALS AND METHOD: Fifty-eight patients aged 19-40 with diagnosed ovarian endometriosis underwent pre-surgical assessment of their ovarian reserve consisting of antral follicle count (AFC), basal ovarian volume (BOV) and FSH level. Twenty-four patients underwent laparoscopic enucleation of the cyst with CO2 laser ablation and thirty-four patients had enucleation with successive electroablation. The ovarian reserve of the patients was reassessed during follow-up assessments three and six months after surgery. RESULTS: In neither group was there a statistically significant decrease of AFC after three or six months. Additionally, in the group that underwent enucleation with electroablation, a significant drop in FSH level was observed after three months. This group was characterized by a statistically significant decrease in BOV at the three- and six-month follow-up assessments. 17% patients had ovarian relapses visible in the ultrasound scan at the six month follow-up assessment. In the group of patients who underwent enucleation with CO2 laser ablation, BOV had not changed significantly, while a high rate of ovarian relapses (39%) was observed. CONCLUSIONS: The lack of significant changes in AFC level after the surgeries suggests an initial positive evaluation of both techniques in the context of ovarian reserve preservation. The detrimental BOV decrease after enucleation with electroablation and high relapse rate after enucleation after CO2 laser ablation shows that further research is needed in order to optimize the laparoscopic techniques of endometriosis therapy.

Female fertility preserving practices at a pediatric unit: a challenge of multiprofessional and multidisciplinary cooperation.

INTRODUCTION: Being able to have children could have an important positive effect on the future lives of pediatric cancer survivors. Working at a cancer institute makes us responsible for filling the gaps in our knowledge in this area of patient care. METHODS: We describe our activities in a series of young females diagnosed with cancer and evaluated for fertility preservation options. We discuss the developed skills and organization as well as the practical difficulties encountered in managing fertility preservation. RESULTS: Since September 2012, laparoscopy and cryopreservation of cortical ovarian tissue has been performed in 16 girls (with ovary transposition in 3, and after several cycles of chemotherapy in 5) and egg banking in 4 young women (before chemotherapy in 2 and several years after treatment in 2). CONCLUSIONS: Recommendations on fertility preservation indicate that discussing the problems early on is crucial to future success. It is unthinkable to simply provide information and offer the opportunity to choose a fertility preserving technique without helping and accompanying patients and their families in their decisions and choices on the matter.

Assessment of transposed ovarian movement: how much of a safety margin should be added during pelvic radiotherapy?

The purpose of this study was to analyze transposed ovarian movement. Data from 27 patients who underwent ovarian transposition after surgical treatment for uterine cancer were retrospectively analyzed. Computed tomography (CT) images including transposed ovaries were superimposed on other CT images acquired at different times, and were matched on bony structures. Differences in ovarian position between the CT images were measured. The planning organ at risk volume (PRV) margins were calculated from the formula of the 90% reference intervals (RIs) and the 95% RI, which were defined as mean ± 1.65 standard deviation (SD) and mean ± 1.96 SD, respectively. The 90% RI in the cranial, caudal, anterior, posterior, left and right directions were 1.5, 1.5, 1.4, 1.0, 1.7 and 0.9 cm, respectively. The 95% RI in the corresponding directions were 1.5, 2.0, 1.7, 1.2, 1.9 and 1.2 cm, respectively. These data suggest that bilateral ovaries need a PRV margin of ∼2 cm in all directions. The present study suggests that a transposed ovary needs the same PRV margin as a normal ovary (∼2 cm). Even after transposition, ovaries should be kept away from the radiation field to take into consideration the degree of ovarian movement.

A new surgical approach of temporary ovarian transposition for children undergoing brachytherapy: technical assessment and dose evaluation.

PURPOSE: We developed a new technique of temporary ovarian transposition (OT) for prepubertal girls undergoing brachytherapy. The aim of this study was to describe it, assess its feasibility and safety and calculate the dose delivered to the ovary in order to prove its efficacy. METHODS: Sixteen prepubertal patients underwent temporary OT for brachytherapy at our center from March 2001 to December 2012. OT was done either by laparotomy or by laparoscopy. In all patients, the ovaries were grasped with an atraumatic forceps and mobilized above the iliac crest level as high as possible without any dissection or division of the ovarian ligaments or of the fallopian tube. They were sutured to the anterior abdominal wall by a transfixing stitch of non-dissolvable suture knotted on the outside of the patient on a pledget. RESULTS: Median age at surgery was 3 years (range: 2-9 years). The integrity of the fallopian tube was respected and not a single ligament was dissected or divided. None of the patients had intraoperative or postoperative complications. The stitches were retrieved after completion of irradiation and the ovaries in all the patients fell back into the pelvis. The calculated median radiation dose to the ovary was 1.4 Gy (range: 0.4-2.4 Gy). CONCLUSIONS: This surgical technique is simple and safe, either by laparotomy or by laparoscopy. It meets the radiation and physical constraints in prepubertal girls with vaginal or bladder RMS. However, longer follow-up is required to assess the ovarian function.

Postoperative recurrence and fertility after endometrioma ablation using plasma energy: retrospective assessment of a 3-year experience.

STUDY OBJECTIVE: To assess recurrence and pregnancy rates in women with ovarian endometrioma treated via ablation using plasma energy. DESIGN: Retrospective non-comparative pilot study including 55 patients treated during 28 months, with prospective recording of data (Canadian Task Force classification II-2). SETTING: Tertiary referral center. PATIENTS: Fifty-five consecutive women with pelvic endometriosis in whom ovarian endometriomas were managed solely via ablation using plasma energy. The minimum follow-up was 1 year. INTERVENTION: Endometrioma ablation using plasma energy. MEASUREMENTS AND MAIN RESULTS: Information was obtained from the database of the North-West Inter Regional Female Cohort for Patients with Endometriosis, based on self-questionnaires completed before surgery, surgical and histologic data, and systematic recording of recurrences, pregnancy, and symptoms. Recurrences were assessed using pelvic ultrasound examination. Mean (SD) follow-up was 20.6 (7.2) months (range, 12-39 months). In 75% of patients, deep infiltrating endometriosis was treated, and 40% had colorectal involvement. Preoperative infertility was recorded in 42% of patients. The rate of postoperative recurrence was 10.9% for the entire series. Of 33 women who wished to conceive, 67% became pregnant, spontaneously in 59%. Time from surgery to the first pregnancy was 7.6 (4.3) months. After discontinuation of postoperative hormone therapy, the probability of not conceiving at 12 months was 0.36 (95% confidence interval, 0.19-0.53), and at 24 months was 0.27 (95% confidence interval, 0.12-0.44). CONCLUSIONS: Recurrence and pregnancy rates are encouraging in that they seem comparable to the best reported results after endometrioma cystectomy. Plasma energy may have an important role in the management of ovarian endometrioma in women seeking to conceive. Patients most in need of surgical procedures that can spare ovarian parenchyma, such as those with bilateral endometriomas or a history of ovarian surgery, may particularly benefit from ablation using plasma energy.

Neither male gonadal androgens nor female reproductive costs drive development of sexual size dimorphism in lizards.

Sexual size dimorphism (SSD) is an extensively studied phenomenon in animals, including reptiles, but the proximate mechanism of its development is poorly understood. The most pervasive candidates are: (1) androgen-mediated control of growth, i.e. a positive effect of gonadal androgens (testosterone) on male growth in male-larger species, and a negative effect in female-larger species; and (2) sex-specific differences in energy allocation to growth, e.g. sex with larger reproductive costs should result in smaller body size. We tested these hypotheses in adults of the male-larger lizard Paroedura picta by conducting castrations with and without testosterone implants in males and manipulating reproductive status in females. Castration or testosterone replacement had no significant effect on final body length in males. High investment to reproduction had no significant effect on final body length in intact females. Interestingly, ovariectomized females and females with testosterone implants grew to larger body size than intact females. We did not find support for either of the above hypotheses and suggest that previously reported effects of gonadal androgens on growth in male lizards could be a consequence of altered behaviour or social status in manipulated individuals. Exogenous testosterone in females led to decreased size of ovaries; its effect on body size may be caused by interference with normal ovarian function. We suggest that ovarian factors, perhaps estrogens, not reproductive costs, can modify growth in female lizards and may thus contribute to the development of SSD. This hypothesis is largely supported by published results on the effect of testosterone treatment or ovariectomy on body size in female squamates.

Preoperative assessment of adnexal mass in adolescent patients.

AIM: Our aim was to assess preoperatively the adnexal mass in adolescent patients. The diagnosis and assessment of these lesions is not easy. That is why we treid to evaluate our results in preoperative assessment of adnexal mass and to compare them with the results of other researchers and clinics working in this field. MATERIALS AND METHODS: We evaluated for 20 years period -550 adolescent patients. We used: biochemical markers, pelvic ultrasound as a second line-test, panel of markers, proteomics, metabolomics, epigenetics, morphological markers, vascular markers and some mathematical models. RESULTS: For the screening of our patients we used mostly combination between Ca125 and ultrasound. Adjuvant chemotherapy was administered in 385 patients (70%). The overall mean follow up was 60 months. We had 66 recurrences (12%) and 16 deaths (3%). The survival rate for patients with with stage I disease was 97% (426 patients) and for patients with advanced stage disease 85% (102 patients). During chemotherapy 70% (269 patients) developed amenorrhea but 93% (358) of these adolescent patients returned to normal function after completion of chemotherapy. 119 healthy live births were recorded in the group with chemotherapy without documentated birth effects. There were only 7 cases with infertility (2%). CONCLUSIONS: The surgical approach in adolescent patients with adnexal mass confined to a single ovary should try to preserve fertility. Advanced stages are not always accompanied by huge and extensive pelvic disease and the uterus and contralateral ovary should be preserved. With the appropriate adjuvant platinum-based combination chemotherapy these adolescent patients have an excellent prognosis and have normal ovarian function and deliver healthy babies. Future studies will give additional light in this field.

Safety assessment of ovarian cryopreservation and transplantation in nude mice bearing human epithelial ovarian cancer.

OBJECTIVE: Nude mice with orthotopic transplantation of human ovarian epithelial cancer were used to investigate screening criteria for paraneoplastic normal ovarian tissue and the security of the freezing and thawing for ovarian tissue transplantation. METHODS: Expression of CK-7, CA125, P53, survivin, MMP-2/TIMP- 2 in paraneoplastic normal ovarian tissues were detected by RT-PCR as well as immunohistochemistry. The tissues of the groups with all negative indicators of RT-PCR, all negative indicators of immunohistochemistry, negative expression of CK-7, CA125 and survivin, positive expression of CK-7, CA125 and survivin, cancer tissues and normal ovarian tissues of nude mice were used for freezing and thawing transplantation, to analyze overt and occult carcinogenesis rates after transplantation. RESULTS: When all indicators or the main indicators, CK-7, CA125 and survivin, were negative, tumorigenesis did not occur after transplantation. In addition the occult carcinogenesis rate was lower than in the group with positive expression of CK-7, CA125 and survivin (P<0.01). After subcutaneous and orthotopic transplantation of ovarian tissues, rates did not change (P>0.05). There was no statistical significance among rates after transplantation of ovarian tissues which were obtained under different severity conditions (P>0.05). CONCLUSION: Negative expression of CK-7, CA125 and survivin can be treated as screening criteria for security of ovarian tissues for transplantation. Immunohistochemical methods can be used as the primary detection approach. Both subcutaneous and orthotopic transplantation are safe. The initial severity does not affect the carcinogenesis rate after tissue transplantation. Freezing and thawing ovarian tissue transplantation in nude mice with human epithelial ovarian carcinoma is feasible and safe.

Long-term follow-up of laparoscopic electrocautery of the ovaries versus ovulation induction with recombinant FSH in clomiphene citrate-resistant women with polycystic ovary syndrome: an economic evaluation.

BACKGROUND: Laparoscopic electrocautery of the ovaries and ovulation induction with gonadotrophins are both second line treatments for women with clomiphene citrate-resistant polycystic ovary syndrome (PCOS). Long-term follow-up after electrocautery versus ovulation induction with gonadotrophins has demonstrated at least comparable chances for a first live born child with a reduced need for ovulation induction or assisted reproduction treatment and increased chances for a second live born child. In this study, we report on the long-term economic consequences of both treatment modalities. METHODS: Between February 1998 and October 2001, we performed a multi-centre randomized controlled trial (RCT) comparing a strategy of laparoscopic electrocautery of the ovaries, followed by clomiphene citrate and gonadotrophins when anovulation persisted, and a strategy of ovulation induction with gonadotrophins in women with clomiphene citrate-resistant PCOS. Eight to twelve years after randomization we performed a follow-up study on reproductive outcome in these women and the fertility treatments they had needed including data on direct medical costs of pregnancy and delivery. Clinical data included number of treatment cycles, live births, miscarriages, ectopic pregnancies and multiple pregnancies. We calculated mean costs per woman after randomization until the first live birth. Confidence intervals (CIs) were estimated by bootstrapping. RESULTS: We obtained data for an economic analysis on 159 of the 168 randomized women (95%). In total, 71 of 83 women (86%) allocated to the electrocautery strategy and 69 of 85 women (81%) allocated to the gonadotrophin strategy had at least one live birth. Given the equivalence between the two treatment strategies in terms of a first live birth-the primary outcome measure-our analysis focused on the cost difference between the two strategies within a mean follow-up time of 8-12 years. The mean costs per first live birth after randomization were €11 176 (95% CI: €9689-€12 549) for the electrocautery group and €14 423 (95% CI: €12 239-€16 606) for the recombinant FSH group, resulting in significantly lower costs (P < 0.05) per first live birth for women allocated to the electrocautery group (mean difference €3247; 95% CI: €650-€5814). CONCLUSION: In women with clomiphene-resistant PCOS, laparoscopic electrocautery of the ovaries results in significantly lower costs per live birth than ovulation induction with gonadotrophins for an at least equal effectiveness.