The impact of IVF on deep invasive endometriosis

Objective: Ovarian hyper-stimulation during IVF is associated with a significant raise in serum estrogens and one may expect detrimental effects on estrogen-dependent diseases such as endometriosis. However, available evidence from large case series of affected women performing IVF is generally reassuring with the possible exception of women carrying deep invasive lesions. On this basis we deemed important investigating more in depth whether women with deep invasive endometriosis could be a subgroup at higher risk of recurrence or disease progression during IVF. Study design: Women with endometriosis who underwent IVF and who had a second evaluation after 3\u20136 months from a failed cycle were retrospectively reviewed. The main inclusion criteria were the presence of deep invasive endometriosis and/or a history of surgery for this form of the disease. The primary aim of the study was to determine the frequency of endometriosis-related complications in the interval between the two evaluations. Secondary aims were pain symptoms and lesion size modifications. Results: Eighty-four women were ultimately selected: baseline ultrasound documented deep invasive lesions in 60 of them. One case of possible endometriosis-related complication was recorded, corresponding to a rate of 1.2% (95%: 0.05%\u20135.5%) for the whole cohort and 1.7% (95%CI: 0.08\u20137.6%) for the subgroup of women with ultrasound detected lesions. This rate appears similar to the reported frequency of endometriosis progression in women not receiving IVF. No significant modifications in pain symptoms or lesions size occurred. Conclusions: Women with deep invasive endometriosis who underwent IVF do not seem to be exposed to a substantially increased risk of recurrence/disease progression. Larger evidence from independent groups is however required for a definitive conclusion

Ovarian stimulation and endometriosis progression or recurrence: a systematic review

Available evidence on the impact of ovarian stimulation on the progression of endometriosis or its recurrence was systematically reviewed. Data from ovarian stimulation alone, or associated with intrauterine insemination (IUI) or IVF, were included. Sixteen studies were selected. Initial case reports (n = 11) documented some severe clinical complications. However, subsequent observational studies were more reassuring. Overall, five conclusions can be drawn: (i) IVF does not worsen endometriosis-related pain symptoms (moderate quality evidence); (ii) IVF does not increase the risk of endometriosis recurrence (moderate quality evidence); (iii) the impact of IVF on ovarian endometriomas, if present at all, is mild (low quality evidence); (iv) IUI may increase the risk of endometriosis recurrence (low quality evidence); (v) deep invasive endometriosis might progress with ovarian stimulation (very low quality evidence). In conclusion, available evidence is generally reassuring (at least for IVF) and does not justify aggressive clinical approaches such as prophylactic surgery before assisted reproductive technology treatment to prevent endometriosis progression or recurrence. However, further evidence is required before being able to reach definitive conclusions. In particular, the potential effects on deep invasive endometriosis and the possible synergistic effect of stimulation and pregnancy are two areas that need to be explored further

Risk factors for monozygotic twinning after in vitro fertilization : a systematic review and meta-analysis

Objectives: To establish the risk factors for monozygotic twin (MZT) and monochorionic twin (MCT) pregnancies after in vitro fertilization (IVF). Design: Systematic review and meta-analysis. Setting: Not applicable. Patient(s): Women who achieved MZT and non-MZT pregnancies through IVF. Intervention(s): Systematic search of Medline from January 1995 to October 2018 with cross-checking of references from relevant articles in English. Main Outcome Measure(s): Possible risk factors for MZT or MCT pregnancies after IVF, comprising extended embryo culture, insemination method (conventional IVF and intracytoplasmic sperm injection [ICSI]), embryo biopsy for preimplantation genetic testing for aneuploidies or for monogenic/single-gene defects (PGT-A or PGT-M) programs, assisted hatching (AH), oocytes donation, female age, and embryo cryopreservation. Result(s): A total of 40 studies were included. Blastocyst transfer compared with cleavage-stage embryo transfer, and female age <35 years were associated with a statistically significant increase in the MZT and MCT pregnancy rate after IVF: (23 studies, OR 2.16, 95% CI, 1.74\u20132.68, I 2 =78%; 4 studies, OR 1.29; 95% CI, 1.03\u20131.62, I 2 =62%; and 3 studies, OR 1.90, 95% CI, 1.21\u20132.98, I 2 =59%; 2 studies, OR 2.34; 95% CI, 1.69\u20133.23, I 2 =0, respectively). Conventional IVF compared with ICSI and assisted hatching were associated with a statistically significantly increased risk of MZT pregnancy (9 studies, OR 1.19, 95% CI, 1.04\u20131.35, I 2 =0; 16 studies, OR 1.17, 95% CI, 1.09\u20131.27, I 2 =29%, respectively). Embryo biopsy for PGT-A or PGT-M, embryo cryopreservation, and oocytes donation were not associated with MZT pregnancies after IVF. Conclusion(s): Blastocyst transfer is associated with an increased risk of both MZT and MCT pregnancies after IVF. Further evidence is needed to clarify the impact of female age, insemination method and AH on the investigated outcomes

Oocyte retrieval difficulties in women with ovarian endometriomas

Research question: What are the frequency, characteristics and consequences of technical diffiiculties encountered by physicians when carrying out oocyte retrieval in women with ovarian endometriomas? Design: We prospectively recruited women undergoing IVF and compared technical difficulties between women with (n = 56) and without (n = 227) endometriomas. Results: In exposed women, the cyst had to be transfixed in eight cases (14%, 95% CI 7 to 25%) and accidental contamination of the follicular fluid with the endometrioma content was recorded in nine women (16%, 95% CI 8 to 27%). Moreover, follicular aspiration was more frequently incomplete (OR 3.6, 95% CI 1.4 to 9.6). In contrast, the retrievals were not deemed to be more technically difficult by the physicians and the rate of oocytes retrieved per developed follicle did not differ. No pelvic infections or cyst ruptures were recorded (0%, 95% CI 0 to 5%). Conclusions: Oocyte retrieval in women with ovarian endometriomas is more problematic but the magnitude of these increased difficulties is modest

The presence of dominant follicles and corpora lutea does not perturb response to controlled ovarian stimulation in random start protocols

The advent of random start protocols to shorten the time needed to store oocytes in women with malignancies has represented an important improvement in the field of fertility preservation. However, Randomized Controlled Trials are difficult to implement in this area and available evidence that supports this approach remains modest. To shed more light on this issue, we compared the follicular development between the ovary carrying the dominant follicle or the corpus luteum and the contralateral resting ovary in 90 women who underwent random start controlled ovarian stimulation (COS). In fact, ovarian response did not differ between the two ovaries. Subgroup analyses according to the phase of the cycle at the initiation of COS, the type of malignancy, the use of letrozole and the magnitude of the ovarian response did not allow to identify any condition showing a difference in the follicular response between the active and the resting ovaries. In conclusion, follicular growth does not seem to be perturbed by the presence of a dominant follicle or a corpus luteum

Diritto Privato

Lo scritto ha ad oggetto i capitoli su modi di estinzione dell'obbligazione diversi dall'adempimento, singoli contratti, possesso, famiglia e trascrizione dei tomi secondo e terzo del manuale Diritto Privato (Utet) in adozione presso alcune Università Italiane e diffuso anche all’estero. I menzionati capitoli si segnalano per una trattazione non meramente istituzionale, ma particolarmente attenta al dato applicativo e giurisprudenziale, che rende il manuale stesso utilizzato largamente per la preparazione all’esame per avvocato e ai concorsi pubblici di secondo livello (magistratura ordinaria e amministrativa.

Magnetic Resonance Imaging Visualization of Vulnerable Atherosclerotic Plaques at the Brachiocephalic Artery of Apolipoprotein E Knockout Mice by the Blood-pool Contrast Agent B22956/1

The aim of this study was to identify, by magnetic resonance imaging (MRI), the ability of the blood-pool contrast agent B22956/1 to detect atherosclerotic plaques developing at the brachiocephalic artery of apolipoprotein E knockout (apoE-KO) mice and to possibly identify vulnerable atherosclerotic lesions. After high-fat feeding for 8 or 12 weeks, MRIs of brachiocephalic arteries were acquired before and after B22956/1 administration; then vessels were removed and analyzed by histology. B22956/1 injection caused a rapid increase in plaque signal enhancement and plaque to muscle contrast values, which remained stable up to 70 minutes. A linear correlation between signal enhancement and macrophage content was found 10 minutes after B22956/1 injection ( p < .01). Signal enhancement and plaque to muscle contrast values correlated with macrophage content 40 minutes after contrast agent administration ( p < .01). Finally, 70 minutes after B22956/1 infusion, plaque to muscle contrast significantly correlated with the percentage of stenosis ( p < .005). B22956/1 administration to high fat-fed apoE-KO mice resulted in a rapid enhancement of atherosclerotic plaques and in a great ability to rapidly visualize vulnerable plaques, characterized by a high macrophage content. These results suggest that B22956/1 could represent an interesting tool for the identification of atherosclerotic plaques potentially leading to acute cardiovascular events

Per scaldare, per cuocere e per produrre. Le strutture da fuoco dell&#8217;abitato etrusco del Forcello di Bagnolo S.Vito (MN) : aspetti tipologici e funzionali

Il Forcello di Bagnolo S.Vito (MN) \ue8 il principale abitato dell\u2019area di espansione etrusca a nord del Po nel VI e V secolo a.C. Si tratta di un insediamento esteso circa 12 ettari dalla struttura pienamente urbana: un impianto ortogonale caratterizzato da assi viari principali e strade minori che si intersecano ortogonalmente e individuano quartieri, occupati da edifici sia di tipo residenziale che produttivo. Le indagini archeologiche, estese su un\u2019area di circa 900 m2 nel nucleo centrale dell\u2019insediamento, si susseguono da oltre trent\u2019anni e hanno permesso di riconoscere nove fasi insediative, definite dallo stratificarsi di attivit\ue0 domestiche, attivit\ue0 artigianali ed eventi catastrofici. L\u2019estensione e la lunga durata delle ricerche hanno permesso di riportare alla luce decine di strutture da fuoco: focolari, forni a fossa per attivit\ue0 pirotecnologiche, resti di fornaci per la cottura della ceramica. L\u2019ampia variet\ue0 tipologica delle strutture da fuoco rinvenute \ue8 cos\uec associata alla funzione degli ambienti in cui esse si trovano, interpretata a sua volta grazie allo studio parallelo dei reperti associati e delle tecniche edilizie.The Forcello site (Bagnolo S. Vito, Mantua) is the main Etruscan settlement north of the Po in the 6th and 5th centuries BC. It is approximately 12-hectare wide, with a fully urban pattern. It\u2019s characterized by an orthogonal plan, defined by main and secondary roads that intersect each other orthogonally and outline blocks, occupied by both residential and productive buildings. The archaeological investigations are carried out in the settlement\u2019s core area, over about 900 m2. After more than thirty years of excavations, nine archaeological phases have been recognized, resulting by the stratification of domestic activities, craft activities and catastrophic events. The extension and the long duration of the researches have brought to light dozens of fire structures: hearths, pit furnaces to cast bronze or to forge iron objects, remains of kilns. The wide typological variety of the fire structures can be evaluated according to the function of the buildings in which they are located, detected by study of archaeological findings and building techniques

Fenretinide treatment accelerates atherosclerosis development in apoE-deficient mice in spite of beneficial metabolic effects

Background and Purpose Fenretinide, a synthetic retinoid derivative first investigated for cancer prevention and treatment, has been shown to ameliorate glucose tolerance, improve plasma lipid profile and reduce body fat mass. These effects, together with its ability to inhibit ceramide synthesis, suggest that fenretinide may have an anti-atherosclerotic action. Experimental Approach To this aim, nine-week-old apoE-knockout (EKO) female mice were fed for twelve weeks a Western diet, without (control) or with (0.1% w/w) fenretinide. As a reference, wild-type (WT) mice were treated similarly. Growth and metabolic parameters were monitored throughout the study. Atherosclerosis development was evaluated in the aorta and at the aortic sinus. Blood and lymphoid organs were further characterized with thorough cytological/histological and immunocytofluorimetric analyses. Key Results Fenretinide treatment significantly lowered body weight, glucose levels and plasma levels of total cholesterol, triglycerides, and phospholipids. In the liver, fenretinide remarkably reduced hepatic glycogenosis and steatosis driven by the Western diet. Treated spleens were abnormally enlarged, with severe follicular atrophy and massive extramedullary haematopoiesis. Severe renal hemosiderin deposition was observed in treated EKO mice. Treatment resulted in a threefold increase of total leukocytes (WT and EKO) and raised the activated/resting monocyte ratio in EKO mice. Finally, atherosclerosis development was markedly increased at the aortic arch, thoracic and abdominal aorta of fenretinide-treated mice. Conclusions and Implications We provide the first evidence that, despite beneficial metabolic effects, fenretinide treatment may enhance the development of atherosclerosis

Fenretinide treatment accelerates atherosclerosis development in apolipoprotein e-deficient mice in spite of beneficial metabolic effects

Aim. Fenretinide, a synthetic retinoid derivative first investigated for cancer prevention and treatment, has been shown to ameliorate glucose tolerance and the plasma lipid profile, and to reduce body fat mass. These effects, together with its ability to inhibit ceramide synthesis, have suggested that fenretinide may display anti-atherosclerotic effects. Methods. To this aim, 9-weeks-old apoE-knockout (EKO) female mice were fed for 12 weeks a Western diet, without (EKO-Ctrl) or with (0.1% w/w) fenretinide (EKO-Fen). As a reference, wild-type (WT) mice were likewise treated. Growth and metabolic parameters were monitored throughout the study. Atherosclerosis development was evaluated in the aorta and at the aortic sinus. Blood and lymphoid organs were further characterized with thorough cytological/histological and immunocytofluorimetric analyses. Results. Fenretinide treatment significantly lowered body weight, glucose levels and plasma levels of total cholesterol, triglycerides and phospholipids. In the liver, fenretinide remarkably reduced hepatic glycogenosis and steatosis driven by the Western diet. Treated spleens were abnormally enlarged, with severe follicular atrophy and massive extramedullary hematopoiesis. Severe renal hemosiderin deposition was observed in EKO-Fen. Treatment resulted in a threefold increase of total leukocytes (WT and EKO) and raised the activated/resting monocyte ratio in EKO-Fen. Finally, atherosclerosis development was markedly increased at the aortic arch (34.4\uc5}7.3% vs 26.1\uc5}5.8%, +32%), thoracic (14.3\uc5}4.9% vs 4.9\uc5}2.1%, +191%) and abdominal aorta (7.6\uc5}3.3% vs 3.3\uc5}1.8%,+130%) of fenretinide-treated mice. Plaque extent was further quantified at the aortic sinus and provided similar results (810.000 \u3bcm2 vs. 540.000 \u3bcm2, +50% in EKO-Fen). Plaques of treated mice were characterized by an increased collagen content and a larger necrotic core, whereas the area occupied by macrophages, foam cells and neutral lipids was comparable between EKO-Fen and EKO-Ctrl. Conclusion. We provide the first evidence that, despite beneficial metabolic effects, fenretinide treatment may prove detrimental for atherosclerosis development