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The purpose of this study was to assess the human papillomavirus (HPV) prevalence in cervical, oropharyngeal and anal samples of the high-risk population of Hungarian female sex workers (FSWs). HPV testing of swab specimens from FSWs (n = 34) using polymerase chain reaction (PCR) methodology was performed. Results were compared with control group (n = 52) matched for age. Questionnaires were used to obtain data regarding participants' sexual behaviour. Data were analysed using SPSS. HPV DNA was detected in at least one location in a great majority of FSWs (82.4%), compared with 46.2% of the general female population (P < 0.05). Both the cervical and the anal samples of sex workers showed higher infection rates than those of controls (64.7% vs. 34.6% and 50.0% vs. 15.4%, respectively, P < 0.05). High-risk HPV prevalence was also significantly higher in sex workers (55.9% vs. 25.0%, P < 0.05). A significantly higher proportion of FSWs had a history of genital warts (26.5% vs. 3.8%, P < 0.05). The results suggest that condom use may not result in adequate protection from HPV infection. The high infection rates among FSWs should be viewed as a priority group for HPV and cervical cancer prevention programmes since they are sources of HPV infection for the general population.

The alarming national data on the mortality and morbidity rates of cervical cancer as well as the results of a Hungarian survey demonstrating adolescents' low level of understanding of human papillomavirus (HPV) infection and HPV vaccination encouraged the authors to conduct an educational intervention. The aim of this survey was to explore the impact of a brief, HPV-focused program on adolescents' knowledge, beliefs and attitudes. A self-administered anonymous questionnaire was completed by 394 male and female adolescents in September, 2010, in Hungary. Half of the students (48.5%) then had a one-off educational intervention on aspects cervical cancer lasting 45 min lesson, while the rest of the participants, the control group, did not have the educational intervention. Three months following the education, both groups were retested using the same questionnaire. Data were analysed using Statistical Package for the Social Sciences (SPSS). Following the education, significant increase was detected in cervical cancer awareness: causal relationship between HPV and cervical cancer (7.9% → 22.1%, p

Objective. The aim of the study was to compare the levels of urinary steroid metabolites of patients with successful in vitro fertilization and patients who failed to achieve pregnancy. Design. Comparison of urinary steroid profiles prior to oocyte pick-up and three weeks after embryo transfer. Setting. University hospital. Sample. Eleven women in the same age range with pregnancy after in vitro fertilization and eleven women who failed to achieve pregnancy. Methods. The standard “long” protocol was used for ovarian stimulation and intracytoplasmic sperm injection for assisted in vitro fertilization. The steroid metabolites in urine samples collected for 24 h were determined by gas chromatography–mass spectrometry. Main outcome measures. Steroid metabolite levels in urine samples determined in the early pregnancy period. Results. The levels of androsterone, etiocholanolone, pregnanediol, tetrahydro-11-dehydrocorticosterone and tetrahydro-corticosterone were significantly higher (p < 0.05) in the urine of women with successful pregnancy three weeks after the embryo transfer, while the levels of tetrahydrocortisone, tetrahydrocortisol, allo-tetrahydrocortisol and α-cortolone became higher in the group of patients with unsuccessful pregnancy. Conclusions. The production of androgens, progesterone and corticoid steroid metabolites is altered in the early pregnancy period after in vitro fertilization.

Hungary takes the fourth place regarding the incidence and the fifth regarding the mortality of cervical cancer among the member countries of the European Union, with 500 deaths due to this preventable illness and nearly 1200 new cases diagnosed every year. Although the vaccines have been available for 3 years, the estimated rate of the female population vaccinated against HPV is approximately 10% in the 12-26-year-age cohort. The aim of this study was to determine factors and motivations affecting the uptake of HPV vaccination among Hungarian adolescents. Examining the effects of some possible sociodemographic predictors (age and gender) and the exposure to health information on HPV vaccine acceptability were also focused on, as well as assessing the most trusted sources of information about sexually transmitted diseases (STDs). A nationwide anonymous questionnaire survey with a sample of 1769 students attending public primary or secondary schools was organised by the authors in 16 Hungarian cities and towns. Data were analysed using the Statistical Package for the Social Sciences (SPSS). Adolescents' awareness of HPV was relatively low. Only 35% of the participants reported they had heard about HPV prior to the survey. Almost 70% of the potentially affected study population had not heard about the vaccine previously. Every fourth student did not believe that vaccination against HPV can prevent cervical cancer. If the vaccination was available free of charge, almost 80% of respondents would request it, but in case they had to pay for it, this number would significantly decrease. Significantly better knowledge and also more positive attitudes towards HPV vaccination was found in relation to the number of information sources. The majority of respondents (62-83%) were open for further information about STDs. The main trusted mediators were school-health services (61.3%), education on health at school (49.2%), health professionals (42.2%) and electronic media (24.6%). Since Hungarian adolescent students expect guidance about STDs principally from school health education, an urgent need for well-designed, HPV-focused educational programmes emerges. Launching such programmes would be especially important for the adolescent population to increase their awareness of the risks associated with HPV infection thus reducing the high incidence of cervical cancer in Hungary in the future.

MAREK E., DERGEZ T., BOZSA S., GOCZE K., REBEK-NAGY G., KRICSKOVICS A., KISS I., EMBER I. & GOCZE P. (2011) European Journal of Cancer Care20, 759–768 Incomplete knowledge – unclarified roles in sex education: results of a national survey about human papillomavirus infections The purpose of this study was to evaluate the awareness of human papillomavirus (HPV) infections both in male and female adults in Hungary. A self-administered, anonymous questionnaire was completed by 785 college students and parents between January and May, 2009. The results were analysed by gender and age. Participants' knowledge about HPV and HPV-associated conditions was relatively incomplete. One-third of the respondents had never heard about HPV prior to the survey. Almost half of the respondents (42%) thought that the only sexual way of spreading HPV was vaginal intercourse, while the role of skin-to-skin contact was disregarded (6%). More than one-third of the participants (38%) believed that condoms give full protection from HPV infection. Encouragingly, the majority of respondents (64%) were open to further information about sexually transmitted diseases. The most trusted sources of information were health professionals. When talking about children, parents attributed the major role in delivering information about sexually transmitted diseases to schools. Primary prevention through carefully planned educational programmes may further raise the awareness about HPV-associated conditions, thus reducing the comparatively high mortality of cervical carcinoma in Hungary.

The potential role of androgen metabolism as co-factors in the development of carcinoma endometrii was investigated.The urinary concentration of 23 androgen, progesterone and corticoid metabolites was quantitatively determined by gas chromatography-mass spectrometry with selected ion-monitoring. We obtained 24-h urine samples from 13 patients with adenocarcinoma endometrii and from 10 age-matched normal female subjects. In the course of the urinary steroid determination, we observed changes in the steroid profiles in the disease examined compared to the same age and same sex control group. Profiling urinary steroids has to give comprehensive information about the synthesis of steroids including the glandular and peripheral steroid metabolisms.The concentrations of 16-hydroxy- dehydroepiandrosterone, pregnanediol and pregnenediol were not significantly different in the two groups. The concentrations of androsterone, etiocholanolone, 11beta-hydroxy-androsterone, 11beta-hydroxy-etiocholanolone, pregnanetriol, pregnenetriol, tetrahydrocortisone, tetrahydro-11-dehydrocorticosterone, tetrahydro-corticosterone, allo-tetrahydro-corticosterone, tetrahydrocortisol, allo-tetrahydrocortisol, alpha-cortolone, beta-cortolone and alpha-cortol were significantly lower in the postmenopausal women with adenocarcinoma than in the controls.The changes in the concentrations of single metabolites point out the important role of steroid group, thus providing help in the recognition and treatment of diseased states.

Objectives The relationship between climacteric osteoporosis and disturbances in menstrual cycle during adolescence was examined. Methods Seven hundred and seventy-one questionnaires were shared out among women visiting the outpatient department for climacteric complaints for the first time between 2001 and 2004. Questions revealed the age, age at menarche and menopause, the regularity or irregularity of menstrual cycle during adolescence and adult ages. The bone mineral density was examined using the Dual Energy X-ray Absorptiometry (DEXA) method on the lumbar spine. Results Six hundred and thirty-five of the 771 questionnaires were suitable for analysis. Osteoporosis was observed in 30.1% of the cases. Age, age at the menarche or at the menopause did not alter in the subgroups with or without osteoporosis. The incidence and severity of osteoporosis were significantly higher in patients reporting secondary amenorrhea during adolescent ages (42.1%; average BMD of the lumbar spine 71.6 ± 3.9), as compared to the patients with normal cycle (30.4%; average BMD of the lumbar spine 84.8 ± 7.8). No correlation between the occurrence of osteoporosis and the frequency of menstrual cycle during adulthood was observed. Conclusions Secondary amenorrhea during the years of adolescence might play a role in the development of more severe osteoporosis in menopause.

Many types of operations are described to create a neovagina in a patient with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, that sometimes result in injury of the surrounding organs. Many trials are detailed in the literature to avoid these complications. Our goal was to examine the benefit of 'endovaginal' sonography during a laparoscopy-assisted Vecchietti operation to avoid bladder injuries.A neovagina was created in 15 women with MRKH syndrome by the method of Vecchietti assisted by laparoscopy. The method was modified with the use of‘endovaginal' sonography, in order to reduce bladder and rectal injuries. The vaginal ultrasound transducer, placed in front of the vaginal dimple, can guide penetration from the perineum into the peritoneal cavity. With this technique, the narrow space between the bladder and rectum can be well identified.All operations were successful, without any complication, forming a well-functioning 8-10 cm long neovagina, allowing easy introduction of two fingers in all cases, and with good quality of sexual life for the couples.Creation of a neovagina by any method in MRKH syndrome may sometimes result in injury of the bladder or rectum due to the narrow space between the bladder and rectum. The placement of the endovaginal ultrasound transducer in front of the vaginal dimple seems to be a promising method to avoid these complications during a laparoscopy-assisted Vecchietti operation.

Background Treatment possibilities of metastatic renal cell carcinoma (mRCC) have recently changed dramatically prolonging the overall survival of the patients. This kind of development brings new challenges for the care of mRCC. Case presentation A 22 year-old female patient with translocation type mRCC, who previously had been treated for nearly 5 years, became pregnant during the treatment break period. Follow-up examinations revealed a dramatic clinical and radiological progression of mRCC in a few weeks therefore the pregnancy was terminated. A few days after surgical abortion, CT examination showed a significant spontaneous regression of the pulmonary metastases, and the volume of the largest manifestation decreased from ca. 30 to 3.5 cm3 in a week. To understand the possible mechanism of this spectacular regression, estrogen, progesterone and luteinizing hormone receptors (ER, PGR and LHR, respectively) immuno-histochemistry assays were performed on the original surgery samples. Immuno-histochemistry showed negative ER, PGR and positive LHR status suggesting the possible angiogenic effect of human chorionic gonadotropin hormone (hCG) in the background. Conclusion We hypothesize that pregnancy may play a causal role in the progression of mRCC via the excess amount of hCG, however, more data are necessary to validate the present notions and the predictive role of LHR overexpression.

Opioid peptides are negative regulators of cell proliferation in several organs including the uterus. In the present study, the ontogeny of the direct inhibitory action of opioid peptides on the proliferation of cultured rat uterine cells was investigated. Uteri of 7, 14, 21, 28, 35 and 60-day-old rats were removed in a sterile way. Tissue blocks were dispersed by limited digestions with trypsin and collagenase. Cells were cultured in enriched Dulbecco's modified Eagle's medium (DMEM). Treatments were present during the entire culture period. Cell densities of the monolayers were determined by counting the cells following trypsinization and trypan blue exclusion. Rat uterine mixed cell cultures grew to confluence within 10 days. The average population doubling time gradually increased with the age of animals. Epidermal growth factor (EGF) increased cell densities of cultures from all age groups. The oestradiol (E2)-responsiveness appeared at 21 days of age. The effect of [D-Met2-Pro5]-enkephalinamide (ENK) was biphasic. ENK and [Met5]-enkephalin (OGF) decreased cell densities of both unstimulated and EGF-stimulated cultures from 7-day-old rats to the same extent. ENK failed to act in 14-day-old animals. From 21 days of age on, the E2- or EGF-stimulated proliferation was inhibited only by ENK and DAMGO, while 30 nm DPDPE, Dynorhin-A, OGF, [Leu5]-enkephalin, beta-endorphin, and morphiceptin were ineffective. The half-inhibitory concentration of ENK was 0.3 nm. The effects of ENK were prevented by concomitant treatment with naloxone. Our novel data demonstrate two different phases of the inhibitory action of opioid peptides on rat uterine cell proliferation during ontogeny with an insensitive interval in between.

Background: Epitheloid trophoblast tumor (ETT) is a tenuous type of gestational trophoblastic disease. Although clinically ETT behave in variable fashion, it is considered as a potentially malignant tumor, fatal malignancy occurs in 10% of the cases. Case and Conclusion: A 41 years old patient, who previously underwent Tompkins operation because of congenital uterine septum was admitted to our clinic due to irregular bleeding. Despite of serum hCG levels under the upper limit of normal, histopathology analysis of D&C obtained endometrial samples confirmed the presence of ETT by immunostainings. Henceforth we performed prompt abdominal hysterectomy and preserved the normal structured ovaries. According to the mullerianosis theory of endometriosis aberrant differentiation or migration could cause spreading of cells throughout the fetal organogenesis of the uterus. These cells in an apoptosis week environment might correlate with the initiation of ETT. As a conclusion we suggest further studies to assess the link between ectopic cells and ETT, to gain a better understanding in the pathomechanism of the tumor.

Endogenous opioid peptides are negative regulators of estradiol-induced uterine cell proliferation. To investigate the possible molecular target site(s) of their anti-mitogenic action, we examined the effect of opioid peptides on epidermal growth factor-induced cell proliferation both in uterine primary cell cultures prepared from adult rats and in human myometrial smooth muscle cell lines. Epidermal growth factor (EGF) significantly increased cell density in both types of cultured monolayers. This EGF-induced stimulation of cell proliferation was blocked by [D-Met(2)-Pro(5)]enkephalinamide in a time-dependent, receptor-mediated manner. The effective concentrations were within the physiological nanomolar range. Enkephalinamide did not have any effect on the basal rate of proliferation of the uterine cells. Our results on this novel physiological cross-talk suggest that shared step(s) of the mechanism of action of estradiol and EGF might be targeted by opioid peptides and not the general machinery of cell proliferation.

To reveal the well known effect of smoking on the incidence of early abortion, the possible effects of cigarette alkaloids on progesterone and estradiol synthesis were investigated. A suspected cause for early spontaneous abortion is corpus luteum insufficiency. The present experiments evaluate the effects of cigarette smoke alkaloids on progesterone and estradiol biosynthesis. Human granulosa cells were obtained from patients undergoing in vitro fertilization and embryo transfer treatment because of infertility. Incubation of the granulosa cells with cotinine, anabasine, with the combination of nicotine, cotinine and anabasine, or with an aqueous extract of cigarette smoke resulted in inhibition of progesterone synthesis. The alkaloids and smoke extract decreased the DNA content of the culture dish. These latter findings suggested a cytotoxic effect of the alkaloids. Both cotinine and anabasine slightly stimulated the synthesis of normalized estradiol. However, nicotine, combination of all three alkaloids, and cigarette smoke extract had no significant influence on estradiol production. Taken together, these data would suggest that cigarette alkaloids inhibit cellular progesterone synthesis both by inhibiting progesterone synthesis and by causing less specific toxic effects to the cell. In contrast, cigarette smoke alkaloids slightly stimulated or had no effect on estradiol production. These concomitant actions of cigarette alkaloids partly explain the higher incidence of early abortion in pregnant women who smoke.

Screening drugs used in obstetrical practice for effects on steroid hormone synthesis revealed that phenobarbital inhibited progesterone synthesis in MA-10 Leydig tumor cells. The inhibition was apparently a drug class effect since it could be reproduced by other barbiturates. Barbiturate blockade was reversible and could be bypassed in the MA-10 cells by using 22-hydroxycholesterol. Human granulosa cell progesterone synthesis was also inhibited in a dose dependent fashion by phenobarbital, secobarbital and barbituric acid. Significant inhibition occurred in dose ranges that would be therapeutic for treating epilepsy. From these data we conclude that barbiturates block steroidogenesis by inhibiting cholesterol transport to the cholesterol side chain cleavage enzyme.

Cervical cancer is the second leading cause of death among female patients with cancer in the world. Our aim was to analyze cervical cancer cases, in the Southwestern Transdanubian Region of Hungary, with regard to human papillomavirus (HPV) genotype and histological and clinical grading. After HPV testing and genotyping, the expressions of eight different pre-microRNAs (miR-21, miR-27a, miR-34a, miR-146a, miR-155, miR-196a, miR-203, miR-221) in formalin-fixed paraffin-embedded (FFPE) primary human cervical cancer samples were evaluated with the help of the LightCycler 480 PCR System (Roche). Statistically significant overexpression of miR-21 (p=0.004), miR-27a (p=0.018), miR-34a (p0.001), miR-155 (p=0.021), miR-196a (p=0.032), miR-203 (p=0.037) and miR-221 (p=0.017) were observed in squamous cell carcinoma, regardless of HPV status and clinical grading. Significant overexpression of miR-21 (p=0.004), miR-27a (p=0.02), miR-34a (p0.001), miR-196a (p=0.027) and miR-221 (p=0.031) was characteristic of HPV-positive squamous cell carcinomas in contrast to adenocarcinomas of the same HPV status.

Background BEV significantly improved the efficacy of front-line CT for OC in the ICON7 and GOG-0218 phase III trials. The global single-arm ROSiA study was designed to assess the safety of BEV-containing therapy, given until progression or for up to 36 cycles, in the context of routine oncology practice. Methods Eligible pts have FIGO stage IIb–IV or grade 3 stage I–IIa epithelial ovarian, fallopian tube or primary peritoneal carcinoma, have received no prior post-surgical therapy for OC, are aged ≥18 years and have ECOG PS 0–2. Prior neoadjuvant CT is permitted. Pts with uncontrolled hypertension, clinical signs/symptoms of GI obstruction, or a history of abdominal fistula, GI perforation or intra-abdominal abscess within the preceding 6 months are ineligible. After definitive surgery, pts receive BEV 15 mg/kg q3w (or 7.5 mg/kg at the investigator's discretion) in combination with 4–8 cycles of CT (paclitaxel [175 mg/m2 d1 q3w or 80 mg/m2 qw) + q3w carboplatin [AUC 5 or 6]). BEV is continued at the same dose as a single agent until disease progression (PD), unacceptable toxicity or for up to 36 cycles. The primary objective is to assess safety (CTCAE v4.03). Secondary endpoints include progression-free survival, overall response rate by RECIST and/or CA-125 response criteria, duration of response and overall survival. The study includes exploration of potential correlations of plasma, tumour and genetic biomarkers with BEV efficacy and toxicity. Results Between Dec 2010 and Apr 2012, ∼1000 pts were enrolled from 35 countries, predominantly Spain (n = 180), Italy (n = 110) and France (n = 101). Baseline characteristics were available from 677 pts as of 30 Jan 2012. Most pts had stage III/IV OC (stage I/II/III/IV: 7%/11%/60%/18%). The majority (93%) received paclitaxel q3w and 94% received BEV at a dose of 15 mg/kg; 14% had received prior neoadjuvant CT. Baseline characteristics from the entire population of ∼1000 pts will be reported, together with details of CT and BEV schedules selected. Conclusions ROSiA should provide valuable new information on the safety of BEV for up to 36 cycles and in pts who have received neoadjuvant CT, as well as enabling extensive translational research. Disclosure N. Colombo: NC has received honoraria for advisory boards and speaker engagements from Roche. F. Selle: FS acts as a Consultant for Roche and PharmaMar. P. Pautier: PP has served on Advisory Boards for Roche and Ipsen. D. Bollag: DB is an employee and holds stocks in F Hoffmann-La Roche Ltd. A.M. Oza: AO has received research funding from Roche. All other authors have declared no conflicts of interest.

The aim of these experiments was to investigate the expression of cyclin D1 and of oestradiol receptors as well as the level of [(3)H]oestradiol binding in leiomyoma and adjacent myometrium from human uteri at different menstrual phases and at an early stage of menopause. [(3)H]oestradiol binding was determined by saturation analysis, while the oestradiol receptor (ER) alpha and beta and cyclin D1 levels were determined by Western blot analysis of 16 samples of human leiomyomas and corresponding myometria at different hormonal stages. In leiomyomas during all phases of the menstrual cycle, ERalpha expression, high affinity oestradiol binding and cyclin D1 expression were all elevated in comparison with adjacent myometrium. ERbeta expression and low affinity oestradiol binding were enhanced in leiomyomas only during the proliferative phase. During menopause, ERbeta expression and low affinity binding were enhanced in leiomyomas, while the ERalpha expression was not significantly enhanced and cyclin D1 levels were similar to that in myometrium. Only the oestradiol binding exhibited any menstrual cycle-related changes. Our data suggest the involvement of cyclin D1 in the growth of leiomyomas during the menstrual cycle. In menopause, there appears to be a switch from ERalpha to ERbeta expression in leiomyomas, and the induction of cyclin D1 is decreased. The regression of tumour may ensue from these changes at menopause.

5541 Background: BEV significantly improved the efficacy of front-line CT for OC in the GOG-0218 and ICON7 phase III trials. The ongoing single-arm ROSiA study, which has completed recruitment of 1039 patients (pts), is assessing BEV + CT in routine oncology practice. Unlike GOG-0218 and ICON7, prior NACT is permitted. We assessed the surgical safety of BEV + CT in the subgroup of pts with prior NACT. Methods: Inclusion criteria include: FIGO stage IIb–IV or grade 3 stage I–IIa epithelial ovarian, fallopian tube, or primary peritoneal carcinoma; no prior post-surgical therapy for OC; and ECOG PS 0–2. Pts with uncontrolled hypertension or clinical signs/symptoms of GI obstruction or history of abdominal fistula, GI perforation, or intra-abdominal abscess in the preceding 6 mo are excluded. Pts in the NA subgroup were enrolled into the study after up to 4 cycles of NACT without BEV. After interval debulking, pts received BEV 15 mg/kg q3w (or 7.5 mg/kg at the investigator’s discretion) in combination with CT (paclitaxel [175 mg/m2 d1 q3w or 80 mg/m2 qw] + q3w carboplatin [AUC 5 or 6]), to a maximum total of 8 cycles including the pre-study NA cycles. Single-agent BEV was continued until progression, unacceptable toxicity, or for up to 36 cycles in total. The primary objective is evaluation of safety (CTCAE v4.03). Additional endpoints include efficacy (including PFS, response rate, OS) and exploratory translational research. Results: Of the 1039 pts enrolled in ROSiA, 150 (14%) had received NACT. Of these, most had stage IIIc (60%) or IV (29%) disease; 65% had residual disease ≤1 cm; and 19% underwent bowel resection. At the data cut-off 22 mo after enrollment began, median follow-up from post-surgery study entry was 12.6 mo; 69 patients (46%) remained on BEV therapy. At cut-off, pts had received a median of 13 cycles of BEV (range 1–31), including 4 cycles (range 1–6) of BEV in combination with CT after surgery. To date, no pts have had grade ≥3 wound-healing complications during study therapy; 1 pt experienced grade 4 GI perforation 10 weeks after surgery (3 weeks after the first BEV dose), which resolved within 4 weeks. Conclusions: NACT followed by BEV + CT was feasible and tolerable. Clinical trial information: NCT01239732.

Objective Recently, 14-3-3 zeta protein was identified as a potential serum biomarker of epithelial ovarian cancer (EOC). The goal of this study was to investigate the clinical potential of 14-3-3 zeta protein for monitoring EOC progression compared with CA-125 and HE4. Design Prospective follow-up study. Setting University of Pecs Medical Center Department of Obstetrics and Gynecology/Oncology (Pecs, Hungary). Population Thirteen EOC patients with advanced stage (FIGO IIb-IIIc) epithelial ovarian cancer that underwent radical surgery and received six consecutive cycles of first line chemotherapy (paclitaxel, carboplatin) in 21-day intervals. Methods Pre- and post-chemotherapy computed tomography (CT) scans were performed. Serum levels of CA-125, HE4, and 14-3-3 zeta protein were detected by enzyme-linked immunosorbent assay (ELISA) and quantitative electrochemiluminescence assay (ECLIA). Main outcome measures Serum levels of CA-125, HE4, and 14-3-3 zeta protein, as well as lesion size according to pre- and post-chemotherapy CT scans. Results Serum levels of CA-125 and HE4 were found to significantly decrease following chemotherapy, and this was consistent with the decrease in lesion size detected post-chemotherapy. In contrast, 14-3-3 zeta protein levels did not significantly differ in healthy postmenopausal patients versus EOC patients. Conclusions Determination of CA-125 and HE4 serum levels for the determination of the risk of ovarian malignancy algorithm (ROMA) represents a useful tool for the prediction of chemotherapy efficacy for EOC patients. However, levels of 14-3-3 zeta protein were not found to vary significantly as a consequence of treatment. Therefore we question if 14-3-3 zeta protein is a reliable biomarker, which correlates with the clinical behavior of EOC.

Background Although some studies have reported a potential connection between ovulation induction therapy (OIT) and malignant ovarian diseases, the results have been inconclusive. In the present study, we sought to determine whether women undergoing OIT at our in vitro fertilization (IVF) clinic, especially those with severe ovarian hyperstimulation syndrome (OHSS) and suspicious cytologic findings, were at risk for developing malignant ovarian tumours after treatment. Methods Patients who underwent OIT at our IVF clinic were enrolled in this study and assessed for any evidence of malignant ovarian tumours. Patients who developed severe OHSS as a result of OIT were treated with a culdocentesis. Cells from the ascitic fluid were cytologically scored for abnormality and malignancy. Peripheral blood samples were obtained from patients with severe OHSS to determine serum levels of the tumour markers (CA-125 and HE4) that were used to calculate the Risk for Ovarian Malignancy Algorithm (ROMA) index. Results Follow-up data were available for 1,353 of the 1,587 patients (85%) who underwent OIT at our IVF clinic between January 2006 and December 2012. Twenty-three patients (1.4%) were hospitalized with OHSS. Culdocentesis was performed 16 times in nine patients with severe OHSS (age range, 23–34 years; mean, 27.1 years). Although cytological examination of the ascitic cells of these patients suggested malignant ovarian neoplasia, over the course of the observation period, the ovarian volume gradually decreased and became normal. Subsequent cytological and histological examinations failed to find evidence of any malignant tumours in these nine patients. None of the 1,353 participants who underwent OIT developed any malignant ovarian tumours during the study period. Moreover, none of the 462 patients who were in our ovarian tumour registry were also participants in the IVF program. Conclusions The presence of atypical cells in the ascitic fluid of women with severe OHSS does not likely indicate malignancy; therefore, radical surgical intervention is not justified. The risk of malignancy is minimal shortly after OIT. At our centre, OIT has not been associated with any cases of ovarian tumour.