Charalampos Chrelias

In Vitro Maturation in Women with vs. without Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis.

Objective To evaluate in vitro maturation (IVM) in sub-fertile women with polycystic ovarian syndrome (PCOS) undergoing in vitro fertilisation (IVF), by comparing outcomes with a control group of non-PCOS. Study design A search strategy was developed for PubMed and studies reporting rates of the following outcomes (live birth; clinical pregnancy; implantation; cycle cancellation; oocyte maturation; oocyte fertilization; miscarriage) between patients with PCOS, PCO and controls undergoing IVM were deemed eligible. The review was conducted in accordance to the PRISMA guidelines and included studies quality was assessed through the Newcastle-Ottawa Quality scale. ORs with their corresponding 95% CIs were calculated for the main analysis and subgroup analyses were performed for PCOS cases vs. controls and PCOS vs. PCO cases. Alternative analyses were performed for live birth and clinical pregnancy, based on cycles and on women. Subgroup analyses for FSH stimulation, hCG priming and type of procedure (IVF/ICSI) were undertaken for all meta-analyses encompassing at least four study arms. Random effects models were used to calculate pooled effect estimates. Results Eleven studies were identified. A total of 268 PCOS patients (328 cycles), 100 PCO patients (110 cycles) and 440 controls (480 cycles) were included in the meta-analysis. A borderline trend towards higher birth rates among PCOS patients emerged (pooled OR = 1.74, 95%CI: 0.99–3.04) mainly reflected at the subgroup analysis vs. controls. Clinical pregnancy (pooled OR = 2.37, 95%CI: 1.53–3.68) and implantation rates (pooled OR = 1.73, 95%CI: 1.06–2.81) were higher, while cancellation rates lower (pooled OR = 0.18, 95%CI: 0.06-0.47) among PCOS vs. non-PCOS subjects; maturation and miscarriage rates did not differ between groups, while a borderline trend towards lower fertilization rates among PCOS patients was observed. Conclusion The present meta-analysis provides preliminary evidence on the effectiveness of IVM as a treatment option when offered in sub-fertile PCOS women, as the latter present at least as high outcome rates as those in non-PCOS.

Potential Pathophysiological Mechanisms of the Beneficial Role of Endometrial Injury in In Vitro Fertilization Outcome.

Successful embryo implantation is a complex process that involves multiple biological mechanisms and reciprocal interactions between the embryo and the proliferated endometrium. In this review, we provide an informative contribution on the pathways underlying the beneficial nature of endometrial injury toward improving implantation rates of embryos conceived and through in vitro fertilization. The evidence published to date are in favor of inducing local endometrial injury in the preceding cycle of ovarian stimulation to improve pregnancy outcomes in women with unexplained and recurrent implantation failure. Endometrial injury triggers a series of biological responses but the findings suggest that no particular pathway is solely adequate to explain the association between trauma and improved pregnancy rates rather than a cluster of events in response to trauma which benefits embryo implantation in ways both known and unknown to the scientific community.

Identification of Women for Referral to Colposcopy by Neural Networks: A Preliminary Study Based on LBC and Molecular Biomarkers

Objective of this study is to investigate the potential of the learning vector quantizer neural network (LVQ-NN) classifier on various diagnostic variables used in the modern cytopathology laboratory and to build an algorithm that may facilitate the classification of individual cases. From all women included in the study, a liquid-based cytology sample was obtained; this was tested via HPV DNA test, E6/E7 HPV mRNA test, and p16 immunostaining. The data were classified by the LVQ-NN into two groups: CIN-2 or worse and CIN-1 or less. Half of the cases were used to train the LVQ-NN; the remaining cases (test set) were used for validation. Out of the 1258 cases, cytology identified correctly 72.90% of the CIN-2 or worst cases and 97.37% of the CIN-1 or less cases, with overall accuracy 94.36%. The application of the LVQ-NN on the test set allowed correct classification for 84.62% of the cases with CIN-2 or worse and 97.64% of the cases with CIN-1 or less, with overall accuracy of 96.03%. The use of the LVQ-NN with cytology and the proposed biomarkers improves significantly the correct classification of cervical precancerous lesions and/or cancer and may facilitate diagnosis and patient management.

Clinical complications after transvaginal oocyte retrieval: A retrospective analysis

There are little systematic data reported in the literature on complications observed after transvaginal oocyte retrieval (OR) guided by ultrasound. We report our experience in 542 in vitro fertilisation cycles. The frequency of severe complications in our patients was 0.72%; of these, two cases were bronchospasm during anaesthesia (0.36%) and two were cases of intraperitoneal bleeding (0.36%); minor vaginal bleeding was the most frequent complication (18.08%), which was treated easily. Through this retrospective analysis, it is evident that clinical suspicion is of particular importance in detecting post-OR complications on one hand, but on the other these complications are rare and most are treated conservatively.

Artificial Intelligence in IVF: A Need

Predicting the outcome of in-vitro fertilization (IVF) treatment is an extremely semantic issue in reproductive medicine. Discrepancies in results among reproductive centres still exist making the construction of new systems capable to foresee the desired outcome a necessity. As such, artificial neural networks (ANNs) represent a combination of a learning, self-adapting, and predicting machine. In this review hypothesis paper we summarize the past efforts of the ANNs systems to predict IVF outcomes. This will be considered together with other statistical models, such as the ensemble techniques, Classification And Regression Tree (CART) and regression analysis techniques, discriminant analysis, and case based reasoning systems. We also summarize the various inputs that have been employed as parameters in these studies to predict the IVF outcome. Finally, we report our attempt to construct a new ANN architecture based on the Learning Vector Quantizer promising good generalization: a system filled by a complete data set of our IVF unit, formulated parameters most commonly used in similar studies, trained by a network expert, and evaluated in terms of predictive power.

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

IntroductionMild 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 MethodsA short narrative review of the existing literature, with emphasis on mild ovarian stimulation clinical and cost effectiveness, as well as treatment limitations.ResultsNumerous 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.ConclusionMild 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.

Using classification and regression trees, liquid-based cytology and nuclear morphometry for the discrimination of endometrial lesions

‘The objective of this study is to investigate the potential of classification and regression trees (CARTs) in discriminating benign from malignant endometrial nuclei and lesions. The study was performed on 222 histologically confirmed liquid based cytological smears, specifically: 117 benign cases, 62 malignant cases and 43 hyperplasias with or without atypia. About 100 nuclei were measured from each case using an image analysis system; in total, we collected 22783 nuclei. The nuclei from 50% of the cases (the training set) were used to construct a CART model that was used for knowledge extraction. The nuclei from the remaining 50% of cases (test set) were used to evaluate the stability and performance of the CART on unknown data. Based on the results of the CART for nuclei classification, we propose two classification methods to discriminate benign from malignant cases. The CART model had an overall accuracy for the classification of endometrial nuclei equal to 85%, specificity 90.68%, and sensitivity 72.05%. Both methods for case classification had similar performance: overall accuracy in the range 94–95%, specificity 95%, and sensitivity 91–94%. The results of the proposed system outperform the standard cytological diagnosis of endometrial lesions. This study highlights interesting diagnostic features of endometrial nuclear morphology and provides a new classification approach for endometrial nuclei and cases. The proposed method can be a useful tool for the everyday practice of the cytological laboratory. Diagn. Cytopathol. 2014;42:582–591.

Feasibility of office hysteroscopy through the “see and treat technique” in private practice: a prospective observational study

PurposeThe purpose of the study was to examine the feasibility of office hysteroscopy through the no-touch “see and treat technique” in a routine basis in private practice.MethodsIn the private practice of two trained gynecologists, women with an indication for further investigation of the uterine cavity were treated with the technique. A total of 112 consecutive women were prospectively allocated to a “no-touch” and “see and treat” technique of hysteroscopy. Neither anaesthesia nor analgesia was used as soon as criteria were met. Hysteroscopy was performed using a rigid 3.4-mm hysteroscope and a medium of 0.9% saline.ResultsTreatment efficacy and patient compliance were evaluated through scores on a visual analogue scale (VAS) for pain, complications and success rates, along with the symphony between hysteroscopic findings and histology. The patients’ pain score on the VAS was low and only in 2 out of 112 cases there was a marked discomfort. In four cases suggested treatment was not successful, because of the fear of the patient. In 60.71% of cases that hysteroscopy was indicated, the uterine cavity was normal. No complications or adverse effects were noted. Apart from one case, there was a full agreement between hysteroscopic findings and histology.ConclusionOffice hysteroscopy is a successful and well-tolerated procedure. Through adequate expertise it should be considered the method of choice in private basis, at the same time when exploration of the uterine cavity is needed.

Comparing classic and newer phenotypes in Greek PCOS women: the prevalence of metabolic syndrome and their association with insulin resistance.

Objective: Recently, it has been debated whether the new polycystic ovary syndrome (PCOS) phenotypes, according to the Rotterdam criteria, share the same metabolic risk with the classic ones (National Institutes of Health 1990). Our study sought to compare the prevalence of metabolic syndrome (MS) and glucose homeostasis disorders in Greek women with classic and new PCOS phenotypes. Materials and methods: Two hundred and sixty-six Greek PCOS women were recruited and divided into groups according to two of the three Rotterdam criteria that they fulfilled. Two subgroups were formed; the first represented the classic phenotypes and the second the new phenotypes. The clinical, biochemical, and ultrasound characteristics of both groups were explored. All subjects were evaluated for MS and underwent a 2-h glucose tolerance test to assess insulin resistance (IR) as measured by the homeostasis model assessment (HOMA-IR), quantitative insulin sensitivity check index (QUIC-KI), and MATSUDA indices. Results: 62.4% of PCOS women were classified as classic NIH phenotypes of which 32 women had MS (prevalence 19.6%). Only 4 patients categorized in the newer phenotypic groups had MS (prevalence 4.1%). Among the subjects with classic phenotypes, 11.7% exhibited impaired glucose tolerance (3-fold higher percentage compared to patients with newer phenotypes). Regarding IR indices, HOMA-IR was significantly higher and QUICKI significantly lower for classic phenotypes. Conclusions: Greek PCOS women with classic phenotypes are at increased risk for MS and impaired glucose homeostasis compared to women with newer phenotypes. A subclassification of PCOS permits the earlier recognition and closer surveillance of women whose metabolic profile indicates potential risks for adverse health outcomes.

Addition of prednisolone and heparin in patients with failed IVF/ICSI cycles: a preliminary report of a clinical trial

Abstract Through a non-randomized clinical trial, we examined the theoretical benefit of the coadministration of low molecular weight heparin (LMWH) and prednisolone on pregnancy outcomes in women with previously failed IVF/ICSI cycles. Fifteen women constituted the study group, and were compared with 19 women receiving LMWH alone and another 18 women with no drugs. Our finding that the combination of the two drugs produced positive differences in terms of embryo quality, pregnancy and live birth rates points to the necessity for adequately powered randomized trials.