Ovarian Hyperstimulation Syndrome after GnRH Agonist Triggering and Freeze-All Protocol? Never Not, Hardly Ever: A Systematic Review of Case Reports.

INTRODUCTION: Ovarian hyperstimulation syndrome (OHSS) is a severe complication associated with controlled ovarian stimulation (COS). GnRH agonist (GnRH-a) triggering is considered an efficient strategy to prevent OHSS in the high-risk patient. METHODS: We performed a review of 11 cases of early and severe OHSS following GnRH-a triggering and freeze-all protocol. Electronic databases were searched from inception of each database until October 2021, to identify case reports and case series that reported OHSS after GnRH-a triggering and freeze-all approach describing patient demographics, COS protocol, and patient outcomes. RESULTS: From the literature review, it is possible to suggest that (1) following GnRH-a triggering, the risk of early and severe OHSS is not totally cancelled; (2) despite it is not possible to predict the event, polycystic ovary syndrome is the most common risk factor; (3) the use of GnRH antagonist starting from the day of PU may represent a valid strategy for preventing OHSS in women with high-risk profile; (4) following the unexpected onset of OHSS, measuring serum levels of human chorionic gonadotropin (hCG) is helpful to exclude an inadvertent exogenous administration or a pregnancy. CONCLUSION: The statement that OHSS risk is eliminated when GnRH-a triggering, a freeze-all strategy, and no hCG in the luteal phase may generate the idea that this event cannot occur. Although rare, these cases have been observed in a relatively short period of time.

Perinatal and obstetric outcomes in singleton pregnancies following fresh versus cryopreserved blastocyst transfer: a meta-analysis.

The transfer of cryopreserved blastocysts is increasing in IVF centres. However, little is known about the perinatal and obstetric outcomes of this procedure. In an attempt to further elucidate these issues, a systematic review and meta-analysis was conducted to compare cryopreserved transfer with fresh blastocyst embryo transfer. The results show that the risk of both preterm (odds ratio [OR] 0.89, 95% confidence interval [CI] 0.80-0.99, P = 0.04) and low birthweight births (OR 0.82, 95% CI 0.68-0.99, P = 0.04) was significantly lower after cryopreserved blastocyst transfer than after fresh blastocyst transfer. The rate of large for gestational age births was significantly higher (OR 1.68, 95% CI 1.55-1.82, P < 0.00001) and the rate of small for gestational age births significantly lower (OR 0.59, 95% CI 0.54-0.65, P < 0.00001) after cryopreserved blastocyst transfer. The transfer of cryopreserved blastocysts was associated with a significantly lower risk of placental abruption (OR 0.58, 95% CI 0.40-0.83, P = 0.003) but a significantly higher risk of Caesarean section (OR 1.21, 95% CI 1.01-1.43, P = 0.03). In conclusion, the perinatal and obstetric outcomes associated with the transfer of cryopreserved blastocysts differ from those associated with fresh blastocyst transfer.

Reproductive function of long-term treated patients with hepatic onset of Wilson's disease: a prospective study.

RESEARCH QUESTION: Wilson's disease (WD) is a disorder of copper metabolism that can cause hormonal alterations. The impact of WD and its therapies on fertility is not well defined. The aim of this study was to evaluate ovarian reserve and sperm parameters in long-term treated WD patients with hepatic onset. DESIGN: WD patients with hepatic onset treated for at least 5 years were compared with healthy controls. Men underwent spermiogram and sperm DNA fragmentation (SDF) analysis. Women were tested for serum FSH, anti-Müllerian hormone (AMH) and sonographic antral follicle count (AFC) in the early follicular phase. Ovulation was monitored with ultrasound and progesterone serum concentrations in the luteal phase. RESULTS: The WD group included 26 patients (12 males), the control group 19 subjects (9 males). All patients apart from four (one male) were responders to WD treatment. Sperm count and morphology were comparable between cases and controls. Sperm motility (total and after 1 h) was significantly lower in cases (44.78 ± 21.65%; 47.85 ± 21.52%) than controls (61.88 ± 11.03; 69.44 ± 11.02%, P = 0.03 and 0.01, respectively). The only non-responder had severe oligo-astheno-teratozoospermia. SDF values were normal in cases and controls. AMH, AFC and FSH did not differ between cases and controls. LH was significantly lower in cases (3.36 ± 1.65 mIU/ml) than controls (6.25 ± 1.03 mIU/ml, P < 0.0001). A non-responder woman who developed neurological signs had a 7-year history of infertility. CONCLUSIONS: WD patients with hepatic onset, diagnosed early and treated, have no impairment in fertility potential even if males show reduced sperm motility and females lower LH values. Only patients with poor disease control have some evidence of impaired fertility.

Improving Reporting of Clinical Studies Using the POSEIDON Criteria: POSORT Guidelines.

The POSEIDON (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number) criteria were developed to help clinicians identify and classify low-prognosis patients undergoing assisted reproductive technology (ART) and provide guidance for possible therapeutic strategies to overcome infertility. Since its introduction, the number of published studies using the POSEIDON criteria has increased steadily. However, a critical analysis of existing evidence indicates inconsistent and incomplete reporting of critical outcomes. Therefore, we developed guidelines to help researchers improve the quality of reporting in studies applying the POSEIDON criteria. We also discuss the advantages of using the POSEIDON criteria in ART clinical studies and elaborate on possible study designs and critical endpoints. Our ultimate goal is to advance the knowledge concerning the clinical use of the POSEIDON criteria to patients, clinicians, and the infertility community.

Circulating Nucleic Acids in Maternal Plasma and Serum in Pregnancy Complications: Are They Really Useful in Clinical Practice? A Systematic Review.

OBJECTIVE: A systematic review was carried out to summarize the available evidence to assess whether circulating nucleic acids in maternal plasma and serum (CNAPS) have the potential to serve as extra and independent markers for the prediction and/or progression monitoring of the most common and severe complications of pregnancy, including preeclampsia, intrauterine growth restriction, preterm delivery, morbidly adherent placenta, gestational diabetes, antiphospholipid syndrome, threatened abortion, intrahepatic cholestasis of pregnancy, and hyperemesis gravidarum. METHOD: A comprehensive literature search of the MEDLINE (PubMed), EMBASE, and ISI Web of Knowledge databases was conducted to identify relevant studies that included amounts of CNAPS in the abovementioned pregnancy complications. RESULTS: Eighty-three studies met the eligibility criteria. The vast majority of studies were conducted on the quantity of total circulating cell free DNA (cfDNA) and cell free fetal DNA (cffDNA), and some were conducted on messenger RNA (mRNA) species. A few studies have instead evaluated the cell free DNA fetal fraction (cfDNAff), but only in a limited number of pregnancy complications. Despite the growing interest and the abundance of the papers available, little information is available for other new CNAPS, including microRNA (miRNA), long noncoding RNA (lncRNA), mitochondrial DNA (mtDNA), and circular RNA. CONCLUSION: Due to the heterogeneity of the populations enrolled, the scarcity of the studies that adjusted the CNAPS values for possible confounding factors, and the difficulty in interpreting the published data, no conclusion regarding the statistical robustness and clinical relevance of the data can be made at present. If assayed at the third trimester, the CNAPS have, however, shown better performance, and could be used in populations already at risk of developing complications as suggested by the presence of other clinical features. Other CNAPS, including miRNA, are under investigation, especially for the screening of gestational diabetes mellitus, but no data about their clinical utility are available. Circulating DNA (cfDNA, cffDNA, and cfDNAff) and mRNA have not been properly evaluated yet, especially in patients asymptomatic early in pregnancy but who developed complications later, perhaps because of the high cost of these techniques and the availability of other predictors of pregnancy complications (biochemical, biophysical, and ultrasound markers). Therefore, from the analysis of the data, the positive predictive value is not available. As regards the new CNAPS, including miRNA, there are still no sufficient data to understand if they can be promising markers for pregnancy complications monitoring and screening, since CNAPS are statistically weak and expensive. It is reasonable to currently conclude that the use of the CNAPS in clinical practice is not recommended.

Novel approaches for diagnosis and management of low prognosis patients in assisted reproductive technology: the POSEIDON concept.

The management of patients with a poor ovarian response (POR) to ovarian stimulation represents a challenging issue in reproductive medicine. Apart from economic burdens, the patient with POR has poor prognosis in assisted reproductive technology (ART), which represents a common cause of drop-out from treatment. To introduce a more nuanced picture of POR, the POSEIDON group developed novel criteria to identify and classify patients with low prognosis who undergo ART. The primary goal of POSEIDON criteria is to offer clinicians a pragmatic system to guide therapeutic management with the mindset to obtain the number of oocytes needed for improving ART success. A novel marker of ART success, namely, the ability to obtain the number of oocytes required for achieving at least one euploid embryo for transfer in each patient, is aligned with the POSEIDON criteria. A novel prediction model (ART Calculator) is developed to help clinicians estimate the POSEIDON marker of success. Furthermore, the POSEIDON criteria can also be used to identify more homogeneous populations to test in interventional trials.

In vitro expansion of human breast cancer epithelial and mesenchymal stromal cells: optimization of a coculture model for personalized therapy approaches.

Molecularly targeted, customized therapies are designed based on the molecular portraits of cancer tissue. The efficacy of targeted therapy in individual patients depends on the contribution of single individual cancer cells within the context of their microenvironment. We have developed an in vitro model of human mammary epithelial-stromal cocultures to answer specific clinical questions related to breast cancer, to provide a tool with which to identify a signature in each breast tumor, and to identify the metabolic molecular targets of therapy in an attempt to optimize the efficacy of targeted therapy in each patient. Fifty-five human breast cancer samples were obtained through surgery. Epithelial and stromal cells were isolated from tissue specimens by differential centrifugation, and cryopreserved. Western blot analysis and RT-PCR were used to identify the tissue-specific expression patterns of cancer cells. Dose-response curves were constructed for the aromatase inhibitor formestane and for herceptin, and a 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide assay was done for combined treatment. We collected and cryopreserved, for future use, viable living cells from 55 breast tumor specimens from which we derived short-term cocultures. The presence of cytokeratins and vimentin was evaluated in 20 samples, and pHER2/neu and aromatase were evaluated in 4 cocultures. Formestane and herceptin had a cumulative growth-inhibitory effect on cocultures expressing epidermal growth factor receptors and aromatase. The in vitro model of human mammary epithelial-stromal cocultures reported herein can be used to examine, and to store, a patient's tumor-derived, living cells that retain the characteristics of the mother-tissue and respond, in vitro, to therapy.

Transcatheter Aortic Valve Implantation Under Angiographic Guidance With and Without Adjunctive Transesophageal Echocardiography.

Although transcatheter aortic valve implantation (TAVI) is still currently guided by transesophageal echocardiography (TEE) in a considerable number of hospitals, exclusive angiographic (Angio) guidance seems a reasonable approach in this setting. To date, however, no studies have directly compared the outcomes of TAVI according to the imaging modality used for procedural guidance. We, therefore, used data from a large multicenter data repository to compare the outcomes of TAVI guided exclusively by Angio and ATEE. All consecutive patients with severe aortic stenosis who underwent TAVI with the CoreValve Revalving System (CRS) in 9 Italian centers from September 2007 to March 2014, dichotomized according to the imaging support used to guide the procedure (ATEE and Angio), were included. Thirty-day and 12-month clinical outcomes were evaluated. Propensity matching analysis was performed to adjust for baseline differences. A total of 625 patients were included (256 and 369 patients were included in the ATEE and Angio groups, respectively). Patients from the ATEE more frequently underwent TAVI under general anesthesia compared with Angio group (37.9% vs 22.8%, respectively, p <0.001). Importantly, ∼80% of the patients experienced mild or even less aortic regurgitation as assessed by angiography after the procedure, without between-group differences. Postdilation and valve-in-valve rates were equivalent (24.7% vs 25%, p = 0.934 and 5.5% vs 3.4%, respectively, p = 0.217). No differences were revealed in the rates of death, cardiovascular death, and stroke or transient ischemic attack at 12-month follow-up. These results were sustained after propensity matching analysis. In conclusion, as long as a comprehensive procedural planning is performed, TAVI with CRS may be performed exclusively under angiographic guidance without the need for associated TEE.

Association between intrafollicular concentration of benzene and outcome of controlled ovarian stimulation in IVF/ICSI cycles: a pilot study.

BACKGROUND: Several studies have shown that exposure to benzene is associated to menstrual disorders, miscarriages and other disorders of the reproductive system. We performed an observational prospective pilot study to evaluate if levels of benzene in follicular fluid were correlated with response to controlled ovarian stimulation. METHOD: Thirty-four normogonadotrophic women undergoing IVF were enrolled. Intra-follicular benzene levels were evaluated by chromatography/mass spectrometry. Based on median benzene level, we divided the study population in two groups: Group A with a "low" intra-follicular benzene concentration (n=19, benzene <0.54 ng/mL) and Group B with a "high" intra-follicular benzene concentration (n=15, benzene ≥ 0.54 ng/mL). The ovarian response to gonadotrophins and the outcome of IVF were analyzed in the two groups. RESULTS: The two groups did not differ in terms of demographic or anthropometric characteristics. Group B had significantly higher basal FSH levels, lower estradiol peak concentration, and fewer oocytes retrieved and embryos transferred (p<0.05). Number of gonadotrophin vials, length of controlled ovarian stimulation and ongoing pregnancy rate were similar in the two groups. CONCLUSION: In conclusion, ovarian response to endogenous and exogenous gonadotrophins appeared to be influenced by intra-follicular benzene levels.

Percutaneous closure of patent foramen ovale in a patient with situs viscerum inversus.

We describe the case of a patient with situs viscerum inversus totalis in whom we performed percutaneous closure of a patent foramen ovale. This case report may represent a further contribution to illustrate instrumental and interventional issues to consider in patients with situs viscerum inversus; it is also an example in which a background in embryology and congenital heart disease may aid cardiologists for the well-tolerated and effective diagnosis and treatment of adult patients with cardiac anomalies.