Placental volume at 11 to 14 gestational weeks in pregnancies complicated with fetal growth restriction and preeclampsia.

OBJECTIVE: The study aims to evaluate the predictive value of first trimester placental volume in pregnancies destined to develop fetal growth restriction (FGR) and preeclampsia (PE). METHODS: Prospective observational study including placentas from 34 FGR, 12 PE, 15 GH (gestational hypertension) pregnancies, and 265 controls. Placental volume (PV) was obtained using VOCAL technique, and a z score was calculated (z-PV). The association of PV with other first trimester variables and maternal characteristics was assessed with Spearman's correlation. RESULTS: PV increased exponentially with crown-rump length (CRL) and was unrelated to maternal factors (weight, age, parity, and smoking status) as well as first trimester uterine artery Doppler, free ß-hCG, nuchal translucency, or fetal heart rate. However, PV was positively associated with maternal height, CRL, PAPP-A, and birth weight. z-PV was a strong predictor for FGR with abnormal fetal Dopplers (AUC = 0.9472, P < 0.001). z-PV provided moderate prediction of FGR with normal fetal Dopplers (AUC = 0.8396, P < 0.001), PE (AUC = 0.8312, P < 0.001), and GH (AUC = 0.7640, P < 0.001). The addition of maternal weight, PAPP-A, ß-hCG, and uterine artery Doppler improved our models. CONCLUSION: At 11 to 14 weeks, PV is an independent predictor of pregnancy complications related to placental insufficiency, and the predictive ability is greater for FGR pregnancies with abnormal fetal Dopplers.

The amount and duration of smoking is associated with aggravation of hormone and biochemical profile in women with PCOS.

We investigated the association between the amount and duration of smoking on biochemical, clinical parameters and the ovarian morphology in women with polycystic ovary syndrome (PCOS). That was a retrospective study. These women were divided into two groups, non-smokers (217) and smokers (92). The amount of cigarettes and duration of smoking was measured in pack-years. Both groups underwent clinical evaluation, biochemical and hormone analysis, transvaginal ultrasound and oral glucose tolerance tests (OGTT). The mean value of the number of cigarettes was 14.8 (±8.8) and the median value of pack-years in the smokers group was 4.0 (1.5-7.5). Smokers group has significantly higher free testosterone (F-T), 17-hydroxyprogesterone (17-OHP), delta 4 androstenedione (Δ4-A), T4, low-density lipoprotein (LDL), and white blood cells (WBC). During correlation of all the above parameters and pack-years, there has been significant positive correlation in F-T and Δ4-A. The participants with more pack-years showed statistically higher values of F-T and Δ4-A. There was also a significant positive correlation between total cholesterol, triglycerides, WBC and pack-years of the participants. Prolactin (PRL) has been inversely associated with pack-years. We concluded that the increase of pack-years aggravated lipid profile, WBC and decreased PRL levels, in PCOS patients.

Metabolic syndrome in Greek women with polycystic ovary syndrome: prevalence, characteristics and associations with body mass index. A prospective controlled study.

PURPOSE: The aim of this study was to estimate the prevalence, to evaluate the characteristics of the metabolic syndrome (MetS) in Greek women with polycystic ovary syndrome (PCOS) and to investigate the correlation of MetS with body mass index (BMI). METHODS: In a prospective controlled study, 230 Greek female patients with PCOS and 155 age-matched healthy controls were enrolled. Diagnosis of PCOS was based on the revised criteria of Rotterdam. Both groups were examined for MetS. Diagnosis of MetS was based on the revised criteria of International Diabetes Federation (IDF). RESULTS: The prevalence of the MetS was 12.6 %, nearly sevenfold higher than the controls. Elevated fasting plasma glucose (7.0 vs. 1.9 %) and elevated triglycerides (10.4 vs. 3.2 %) were more frequent in the PCOS cohort (p < 0.05). Women with PCOS presented statistically higher BMI in comparison with the controls (p < 0.001). Subsequently, the prevalence of MetS was estimated in three groups: normal, overweight and obese subdivided according to BMI. The latter two groups showed significant differences compared with the healthy controls (24.5 vs. 8.8 %, p = 0.050). CONCLUSION: In conclusion, this study showed high prevalence of MetS and increased BMI in Greek PCOS women. In addition, it demonstrated the higher prevalence of MetS in obese PCOS women in comparison with the controls. These results are placing them at increased risk for cardiovascular disease and diabetes in the future and underline the necessity of periodic screening, appropriate diet and exercise program.

Predicting fetal growth deviation in parous women: combining the birth weight of the previous pregnancy and third trimester ultrasound scan.

AIM: To investigate the value of the birth weight of the previous pregnancy (BW1) alone and combined with the third trimester ultrasonographically estimated fetal weight (EFW) and Doppler studies in the prediction of small (SGA) and large for gestational age (LGA) neonates in the index pregnancy (BW2). METHOD: Some 1298 parous women with uncomplicated singleton pregnancies who had a third trimester ultrasound scan were considered as samples in this retrospective cohort study. Maternal and pregnancy characteristics, BW1, EFW, umbilical artery, and middle cerebral artery pulsatility indices were investigated as predictors of SGA and LGA. RESULTS: BW1, maternal weight, mode of conception, and smoking status were associated with BW2 (R2=0.39) with BW1 being the strongest predictor (R2=0.37). The addition of EFW conferred significant improvement (R2=0.63), whereas the addition of the Doppler indices did not. The sensitivity of BW1 alone in the prediction of SGA was 75% for 25% screen positive rate and increased to 92% with the addition of EFW. The equivalent figures for LGA were 68% and 93%, respectively. CONCLUSIONS: BW1 used as a continuous variable is predictive of growth deviations in the index pregnancy. Incorporating EFW enhanced the sensitivity for the detection of both conditions.

E-selectin, resistin and reactive oxygen species levels in GnRH -agonist and -antagonist protocols in IVF/ICSI: a prospective cohort study.

PURPOSE: To compare E-selectin, resistin and reactive oxygen species (ROS) levels in serum and follicular fluid (FF) of subfertile women undergoing Controlled Ovarian Hyperstimulation (COH) during IVF/ICSI cycles, using GnRH-agonist and -antagonist protocols. METHODS: In this prospective cohort study, 85 subfertile women undergoing IVF/ICSI were included. Participants underwent the GnRH-agonist and -antagonist protocols; and blood samples were collected at three time points: basic (at start of COH), on the day of hCG and at oocyte retrieval (OR); and from the FF from the first follicle aspirate. Clinical and IVF cycle characteristics, were compared between groups, together with the levels of E-selectin, resistin and ROS in serum and FF, through ELISA. Their prognostic value on pregnancy outcomes was examined. RESULT(S): Examining molecules levels are increasing in serum, from start of COH until OR, irrespectively of the protocol used; FF levels at OR were similar to those in serum at that day. Resistin FF levels were lower in GnRH agonists, compared with the antagonist protocol. Resistin levels at start of COH were associated with clinical pregnancy rates, and this remained significant following adjustment for age, BMI and IVF protocol used, while values of >13.5 ng/ml were associated with a six times greater odd of a pregnancy. CONCLUSION: E-selectin, resistin and ROS levels are increasing during COH, reaching their highest values at OR, with comparable values measured in the FF at that time. Resistin values >13.5 ng/ml are linked with a 6-fold increase on the odds of a pregnancy.

Towards detecting open spina bifida in the first trimester: the examination of the posterior brain.

INTRODUCTION: Our aim was to examine the value of indirect signs of open spina bifida in the mid-sagittal view of the posterior brain at the 11-13 weeks' ultrasound examination and to summarize the current evidence for the first-trimester diagnosis of spina bifida. METHODS: This was a prospective study in routine obstetric population. The presence of four almost parallel lines (four-line view) in the posterior brain was recorded. Biparietal diameter (BPD), intracranial translucency (IT) and cisterna magna (CM) were measured. The ratio of IT to CM (R ratio) was calculated. RESULTS: 2,491 pregnancies were examined prospectively. Updated reference ranges for IT and CM were constructed. There were 3 cases with open spina bifida, and the four-line view was abnormal in 2 of them. The abnormal fetuses had smaller BPD as well as pronounced reduction in the CM and increase in the R ratio. DISCUSSION: Examination of the posterior brain was feasible in all fetuses in the setting of the routine 11-13 weeks' ultrasound examination. Indirect signs of spina bifida are visible in the mid-sagittal view of the posterior brain, and the assessment of these structures can be a reliable tool in the early identification of this abnormality.

Epidemiological and clinicopathological characteristics of BRCA-positive and BRCA-negative breast cancer patients in Greece.

PURPOSE: BRCA mutation carriers can benefit from targeted clinical interventions. On the other hand, families with evident aggregation of breast cancer (BC) cases and a BRCA-negative genetic test can still be considered as of elevated risk, since the underlying genetic factor remains unidentified. In the present study, we compared clinical and demographic characteristics between BRCA1 mutation carriers (BRCA1mut) and non-carriers (non-BRCA1) in a Greek group of BC patients (n=321). METHODS: Data were collected and analyzed from 321 women with BC, with 131 patients screened for pathogenic mutations in the high-penetrant genes BRCA1 and BRCA2. Collected data included demographics, pedigrees, tumor histopathology and immunohistochemistry findings. RESULTS: In BRCA1mut patients, their mothers and grand- mothers were diagnosed at a younger age compared to non-BRCA1-carriers. Additionally, BRCA1mut patients were diagnosed with mainly estrogen receptor (ER) negative (p<0.001), Her-2 negative (p<0.05) and triple negative (p<0.01) tumors. The youngest generation was diagnosed with familial breast cancer (FBC) 9.7 years earlier than their mothers (p<0.001). Age at BC diagnosis negatively correlated with the nuclear grade of breast tumors (r=-0.3, p<0.05). Among parous individuals, the number of full-term pregnancies significantly correlated with the age at BC onset (r=0.19, p<0.05). CONCLUSION: Despite their similarities, FBC cases with identified BRCA1 mutations exhibit a clearly distinct profile. We have identified an anticipation effect in FBC patients, with significantly reduced age at diagnosis in younger generations. Increased parity seems to prevent early BC onset. This is the first study comparing clinical and demographic characteristics of FBC BRCA1mut and non-carriers in a Greek cohort.

Screening for birth weight deviations by second and third trimester ultrasound scan.

OBJECTIVE: The aim of this article was to predict small for gestational age (SGA, at or less than the fifth birth weight percentile) and large for gestational age (LGA, at or greater than the 95th birth weight percentile) fetuses by using maternal and fetal parameters from the second and third trimester ultrasound examinations. METHOD: This article is a retrospective cohort study on 1979 singleton pregnancies that had a routine 20 to 24 weeks anomaly and a 30 to 34 weeks growth ultrasound scans. SGA delivered before 30 gestational weeks were excluded. RESULTS: Second trimester estimated fetal weight (EFW2 ), uterine arteries pulsatility index (PI), and maternal pregnancy characteristics were predictive for SGA (SGA second trimester model: R(2) = 0.225, area under the curve [AUC] = 0.815) and LGA (LGA second trimester model: R(2) = 0.203, AUC = 0.793). Third trimester EFW (EFW3 ), EFW2 , uterine arteries PI2 , umbilical PI, and maternal pregnancy characteristics improved the prediction of SGA (SGA combined model: R(2) = 0.423, AUC = 0.896) and LGA (LGA combined model: R(2) = 0.383, AUC = 0.882). Contingent screening with risk stratification by the second trimester model performed equally well for SGA (AUC = 0.882) and LGA (AUC = 0.861) as the combined models. CONCLUSION: Second trimester model performs well in the prediction of SGA and LGA. The addition of third trimester scan offers substantial improvement. Contingency screening is feasible with similar effectiveness.

The contribution of sildenafil (Viagra) to ovarian stimulation with gonadotropins in a woman with poor ovarian response.

We aim to present the first case of a pregnancy achieved by administering sildenafil (Viagra) to a woman not responding to controlled ovarian hyperstimulation (COH) with the sole use of gonadotropins. A 37-year-old woman underwent COH, as part of an intracytoplasmic sperm injection (ICSI) cycle, with the combination of r-FSH and HMG for 13 d, without evidence of follicular growth. The addition of oral sildenafil at a dose of 50 mg per day for a total of five doses improved the ovarian response and resulted in the retrieval of 10 oocytes. Three embryos were transferred to the uterine cavity resulting in a successful pregnancy and, eventually, the delivery of a healthy neonate. Conclusively, the use of sildenafil as an adjunct to COH protocols may enhance ovarian response in a woman with poor ovarian response (POR) and merits further research.

The diagnostic accuracy of E6 & 7 mRNA detection as a primary screening test for the detection of severe cervical lesions.

PURPOSE: This prospective accuracy study aimed to assess the diagnostic accuracy of nucleic acid sequence amplification (NASBA) and flow cytometry for E6/7 human papillomavirus (HPV) mRNA detection as a primary screening test compared to cytology in the triage of severe cervical intraepithelial neoplasia (CIN) lesions. METHODS: 1083 women referred to our outpatient gynecology clinics for a routine Pap test were recruited. Residual material of the Pap smears was tested by NASBA and by flow cytometry for E6/7 mRNA expression. Biopsy results were used as reference standards. The accuracy indices of both techniques and of NASBA type-16 HPV were assessed for the detection of CIN2+ lesions and were compared to cytology. RESULTS: An increased lesion severity was associated with increased positivity rates of both NASBA and flow cytometry tests (x(2), p<0.001). A positive correlation between NASBA and flow cytometry was identified when these methods were examined with the Phi coefficient (value 0.369, 95% confidence interval [95%CI] : 0.307-0.426). Furthermore, NASBA (89.7 vs 57.7%, p<0.0005) and flow cytometry (77.3 vs 57.7%, p<0.0005) exhibited higher specificity rates than cytology. However, their sensitivity rates did not exceed those of cytology (NASBA:69.8 vs 84.6%, p=0.051; flow cytometry: 69.12 vs 84.6%, p=0.043). CONCLUSIONS: Both NASBA and flow cytometry exhibited increased specificity for the triage of CIN2+ lesions. However, their relatively lower sensitivity and higher positivity rates when compared to cytology do not make them ideal for a primary screening test. Hence, the role of mRNA detection in the screening for severe cervical lesions remains to be clarified.

Ovarian SAHA syndrome is associated with a more insulin-resistant profile and represents an independent risk factor for glucose abnormalities in women with polycystic ovary syndrome: a prospective controlled study.

BACKGROUND: SAHA syndrome is characterized by the tetrad: seborrhea, acne, hirsutism, and androgenetic alopecia. No previous study has examined the prevalence of glucose abnormalities in ovarian SAHA and explored whether it may be an independent risk factor for glucose abnormalities. OBJECTIVE: In a prospective controlled study, we investigated the spectrum of glucose abnormalities in ovarian SAHA and explored whether it is associated with a more insulin-resistant profile. METHODS: In all, 316 patients with a diagnosis of polycystic ovary syndrome (PCOS) (56 with SAHA) and 102 age-matched healthy women were examined and underwent a 2-hour oral glucose tolerance test. Serum glucose homeostasis parameters, hormones, and adipokines were determined. RESULTS: SAHA prevalence was 17.7% in patients with PCOS and predominance of the severe PCOS phenotype. Ovarian SAHA was independently associated with a more insulin-resistant profile (higher homeostatic model assessment of insulin resistance score, lower quantitative insulin sensitivity check index [QUICKI] and MATSUDA indices, and relative hypoadiponectinemia), and represented an independent risk factor for glucose abnormalities regardless of anthropometric features, age, and PCOS phenotype. LIMITATION: There was no performance of skin biopsies. CONCLUSION: The prompt recognition of SAHA syndrome in women with PCOS permits an earlier diagnosis and surveillance of metabolic abnormalities, especially in Mediterranean PCOS population exhibiting a lower prevalence of glucose abnormalities.

Performance of the ultrasound examination in the early and late third trimester for the prediction of birth weight deviations.

OBJECTIVES: This study aimed to define the optimal gestational age in the third trimester, early (30-33 weeks + 6 days) versus late (34-37 weeks), for performing an ultrasound examination for fetal biometry to predict birth weight deviations: small for gestational age (SGA ≤ 5th centile) and large for gestational age (LGA ≥ 95th centile) neonates. METHODS: We used an observational cross-sectional study in uncomplicated singleton pregnancies that had a third trimester ultrasound for fetal biometry and umbilical and middle cerebral fetal Doppler studies. Estimated fetal weight and fetal Doppler parameters were the examined variables for the prediction of SGA and LGA. RESULTS: Three thousand six hundred ninety women had an early examination, and 2288 women had a late one. For a screen-positive rate of 10%, estimated fetal weight achieved 58% and 53.4% sensitivity for the prediction of SGA [area under the curve (AUC) = 0.8578, p < 0.001] and LGA (AUC = 0.8547, p < 0.001), respectively, by the early examination. Accordingly, the sensitivities significantly increased to 75.2% and 63.2% for the prediction of SGA (AUC = 0.9074, p < 0.001) and LGA (AUC = 0.8782, p < 0.001), respectively, by the late examination. The inclusion of the Doppler indices did not improve the predictive models. CONCLUSIONS: A late third trimester ultrasound was superior in the prediction of SGA and LGA, and this improvement was more pronounced for the prediction of SGA.

Assessment of the posterior brain at 11-14 weeks for the prediction of open neural tube defects.

OBJECTIVE: To evaluate the routine midsagittal view of the posterior brain at the 11-13 weeks' ultrasound examination, for predicting open neural tube defects. METHODS: Posterior brain was examined midsagittally for normality of the four-line view (upper and lower border of the brain stem, the choroid plexus of the fourth ventricle and the occipital bone). Intracranial translucency and cisterna magna (CM) were measured. RESULTS: The posterior brain was assessed in 1330 cases. The four-line view was normal in all but one case. In the two cases of open spina bifida contained in the study population, intracranial translucency was within normal range. The CM and the four-line view were normal in the first case, whereas in the second case, the four-line view was abnormal, and CM was obliterated and impossible to measure. No other cases of abnormal four-line view were observed in the study population. CONCLUSION: Obliteration of the CM appears to be the most consistent early sign of open neural tube defects. Attention should focus on either measuring the cisterna magna or simply observing the presence of four lines in the midsagittal view of the posterior brain. However, these early signs of brain herniation are not present in all abnormal cases.

Reproducibility study of crown-rump length and biparietal diameter measurements in the first trimester.

OBJECTIVE: This study aims to investigate the intra-observer and inter-observer variability of crown-rump length (CRL) and biparietal diameter (BPD) measurements in the first trimester. METHODS: A prospective observational study on 592 fetuses between 8 and 14 gestational weeks was conducted. Intra-class correlation coefficients (ICCs) were computed, and Bland-Altman analysis was carried out. RESULTS: The ICCs (95% confidence interval) and the 95% limits of agreement, expressed as a percentage of the average, for CRL's intra-observer and inter-observer variability were 0.979 (0.974-0.982, p < 0.001), +8.53% to -8.376%, and 0.968 (0.952-0.978, p < 0.001), +9.06% to -7.69%, respectively. The corresponding figures for BPD were 0.981 (0.977-0.984, p < 0.001), +7.41% to -7.51%, and 0.968 (0.952-0.978, p < 0.001), +6.65% to -7.25%. After conversion in days, the ICCs and 95% limits of agreement for CRL's intra-observer and inter-observer variability were 0.983 (0.980-0.986, p < 0.001), +2.88% to -2.84%, and 0.971 (0.957-0.980, p < 0.001), 2.83% to -2.60%, respectively. The corresponding figures for BPD were 0.982 (0.979-0.986, p < 0.001), +3.36% to -3.40%, and 0.968 (0.953-0.978, p < 0.001), +3.06% to -3.38%. CRL's standard deviation of the differences increased with gestation for intra-observer (r = 0.289, p < 0.001) and inter-observer (r = 0.197, p = 0.023) variability. CONCLUSION: The BPD and CRL are highly reproducible measurements. CRL's measurement error increased with the magnitude of CRL, whereas BPD's reproducibility was not affected by gestational age.

Third trimester ultrasound for the prediction of the large for gestational age fetus in low-risk population and evaluation of contingency strategies.

OBJECTIVE: Evaluation of the effectiveness of third trimester fetal biometry and Doppler studies in predicting the birth of a large for gestational age neonate (LGA ≥ 95(th) centile). Assessment of the value of integrated models (combining maternal characteristics, first trimester parameters, third trimester fetal biometry) and the usefulness of contingency strategies. METHOD: Observational cross-sectional study on 2308 uncomplicated singleton pregnancies examined at 11 to 14 weeks and at 30 to 34 weeks. RESULTS: Ultrasound estimated fetal weight (EFW, area under the curve (AUC) = 0.83) was the best single predictor of LGA. Maternal weight, delta nuchal translucency and EFW were independent predictors for the integrated model, but the latter was not statistically better (AUC = 0.84) than using EFW alone. The detection rates for LGA were 72.5% and 73.7% for a 25% screen positive rate, by EFW and the third trimester integrated model respectively. A contingency strategy of rescanning 50% of the population in the third trimester according to the risk estimation by a first trimester prediction model results in detection rate of 64.7% for LGA for the same 25% screen positive rate (AUC = 0.78). CONCLUSIONS: Third trimester ultrasound is an effective screening modality for identifying fetal macrosomia. A contingency strategy utilizing first trimester parameters can reduce the need for unnecessary examinations.

The diagnostic accuracy of two methods for E6&7 mRNA detection in women with minor cytological abnormalities.

OBJECTIVE: To examine the diagnostic accuracy of nucleic acid sequence based amplification (NASBA) and flow cytometry for E6&7 human papillomavirus (HPV) mRNA detection in the triage of minor cytological abnormalities. DESIGN: Prospective diagnostic accuracy study. SETTING: Gynecology outpatient clinics of a university hospital. POPULATION: 472 women with low-grade squamous intraepithelial lesion (LSIL) or atypical squamous cells of undetermined significance (ASCUS). METHODS: Residual material of the liquid-based smears was tested by NASBA and by flow cytometry for E6&E7 mRNA expression. Histological diagnosis was used as reference standard. MAIN OUTCOME MEASURES: Accuracy indices of the two techniques and of type 16-specific NASBA for the detection of cervical intraepithelial neoplasia (CIN) 2+ and CIN3+, accuracy indices at age >35 years, correlation between NASBA and flow, comparison between integrated and episomal high-risk HPV infection for risk of CIN2+. RESULTS: Both tests showed increased positivity rates with increasing severity of the lesion (p < 0.05, chi-squared test for trend). There was a positive correlation between NASBA and flow results (phi coefficient = 0.325). NASBA-positive cases were more likely to have CIN2+ than were NASBA-negative/DNA-positive for types 16, 18, 31, 33, 45 (25/73 vs. 4/52, p= 0.0004; Fisher's exact test). In the LSIL group the NASBA accuracy indices for CIN3+ were: sensitivity 75%, specificity 78.7% and positivity rate 20.8%, and for flow 77.8%, 64.5% and 35.9%, respectively. CONCLUSIONS: NASBA has favorable specificity and positivity rates for triaging LSIL prior to colposcopy. A relatively low sensitivity warrants cytological surveillance of the NASBA-negative LSILs. Flow cytometry does not perform as well overall.

The prevalence of glucose metabolism abnormalities in Greek women with polycystic ovary syndrome.

The prevalence of glucose metabolism abnormalities in PCOS women worldwide varies between 10 and 40% but there are no data in Greek PCOS women. In this retrospective study the prevalence of glucose abnormalities and the indices of insulin resistance (IR) and whole-body insulin sensitivity were estimated in a Greek population with PCOS. Impaired glucose tolerance (IGT), impaired fasting glucose (IFG) and type 2 diabetes mellitus (t2DM) were calculated. The prevalence of IGT, IFG and t2DM in our PCOS population was 7.6, 5.1 and 1.7%, respectively. The total prevalence of glucose abnormalities was estimated as 14.1%. The prevalence of t2DM was three- to four-fold higher than in the general Greek female population of the same age as this was estimated by 2, recently published studies. PCOS women with increased BMI and waist circumference and age greater than 30 years, present more severe IR and decreased whole-body insulin sensitivity. Our data indicates a relatively high prevalence of glucose intolerance and t2DM in a Greek population with PCOS. Obese women with PCOS are in higher risk to develop glucose abnormalities and probably t2DM later in life and therefore every woman diagnosed with PCOS should undergo a 2-h post load OGTT.

A short narrative review of the feasibility of adopting mild ovarian stimulation for IVF as the current standard of care.

INTRODUCTION: Mild ovarian stimulation has been conceived, proposed and implemented in clinical practice as a safer and cheaper alternative to conventional strategies of controlled ovarian hyperstimulation in preparation for in vitro fertilization (IVF). Our aim was to summarize the key evidence on this topic and explore its possible role as the standard treatment option for women undergoing IVF. MATERIALS AND METHODS: A short narrative review of the existing literature, with emphasis on mild ovarian stimulation clinical and cost effectiveness, as well as treatment limitations. RESULTS: Numerous studies highlight mild ovarian stimulation's favorable characteristics with respect to oocyte/embryo quality, reduced patient risk, and ease of intervention. There is, however, a need for high-quality laboratory environment. Limitations regarding poor responders, older women, or those seeking ovarian stimulation for non-infertility indications should also be considered. Finally, outcomes on the cumulative success rates and the cost effectiveness of mild ovarian stimulation remain inconclusive. CONCLUSION: Mild ovarian stimulation protocols for IVF should currently be implemented only in carefully selected populations. Further research is needed to clarify the remaining controversies in this IVF approach.

Controversies in the management of endometriomas in patients undergoing assisted reproduction.

INTRODUCTION: The presence of an endometrioma has been proposed to affect the ovarian function in a negative way. Our aim was to present the key evidence on multiple aspects of endometriomas' management in subfertile couples scheduled for assisted reproduction technologies (ART). MATERIALS AND METHODS: A critical review of the existing literature was performed focusing on the need of endometrioma treatment prior to ART, the relevant options, the potentially participating surgeon's characteristics and the socioeconomic perspective. RESULTS: To date, we have no definitive data to suggest whether the damage to the ovaries observed in women with endometriomas may be related to the mere presence of the cyst, the surgical procedure to remove it, the combination of the two, or factors currently unknown. Moreover, there is no conclusive evidence that, for subfertile couples, removal of endometriomas increases the chance of having a baby. The uncertainty regarding the best treatment strategy and factors such as the limited number of tertiary centers for laparoscopic surgery throughout the world seems to further complicate the decision. CONCLUSIONS: Until research addresses the current "grey areas", the management of endometriomas in patients undergoing ART should be individualized and take into consideration numerous parameters.

Genetic variability and phylogeny of high risk HPV type 16, 18, 31, 33 and 45 L1 gene in Greek women.

The present study explores nucleotide variability, phylogeny and association with cervical neoplasia in high risk HPV types 16, 18, 31, 33 and 45 collected from Greek women. Of the 1894 women undergoing routine cervical cytology examination, 160 samples test positive for single infections of HPV type 16 (n = 104), HPV 31 (n = 40), HPV 33 (n = 7), HPV 18 (n = 5), and HPV 45 (n = 4) were typed by microarrays method, amplified by PCR then sequenced and phylogenetically analyzed. For HPV 16, 9 variants with nucleotide variations were included into the study. For HPV 31, 33, 18 and 45, nucleotide variations were identified in 6, 4, 2 and 3 variants, respectively. The Bayesian inference and Maximum Parsimony methods were used in order to construct the phylogenetic trees. When types were analyzed independently HPV 16 (European and non-European) and HPV 18 (African and non-African) formed distinct clades. The genomic characterization of HPV variants will be important for illuminating the geographical relatedness and biological differences and for the determination of their risk.