To define predictors of malignancy after Testis sparing surgery (TSS) in patients referring to a fertility center with incidental small testicular lesions. Sub analyses were performed to assess ...predictors of Leydig cell hyperplasia and Leydig cell tumor.
We performed a retrospective analysis of a single institutional database including patients treated with TSS between 2002 and 2020. All patients who underwent TSS as a first line surgical approach for incidentally detected lesions found during fertility evaluation were included.
Data of 64 patients were collected. The median follow up was 58 months and no recurrences were observed. At univariable logistic regression multifocal lesions, hypervascularization, microlithiasis, age and lesion size were significantly associated with malignancy. At multivariable logistic regression lesion dimension, hypervascularization and multifocal lesions were predictors of malignancy. Lesions smaller than 5 mm proved to be benign in 96.6% of the cases (32/33). Intraoperative color of the lesion and US pattern of vascularization were predictors at multivariable logistic regression for Leydig cell hyperplasia and Leydig cell tumor.
Ultrasonographic characteristics and intraoperative appearance of the lesion can predict the malignant nature of small testicular lesions, guiding their surgical management in patients referring to a fertility center. Based on our experience, clinicians may safely perform TSS in carefully selected patients.
Abstract
Elagolix, an orally active non-peptidic GnRH antagonist, has been approved by the Food and Drug Administration for the management of moderate to severe pain associated with endometriosis. As ...the degree of ovarian suppression obtained with elagolix is dose-dependent, pain relief may be achieved by modulating the level of hypo-oestrogenism while limiting side effects. Elagolix may thus be considered a novelty in terms of its endocrine and pharmacological properties but not for its impact on the pathogenic mechanisms of endometriosis, as the target of this new drug is, yet again, alteration of the hormonal milieu. Given the oestrogen-dependent nature of endometriosis, a reduction of side effects may imply a proportionate decrease in pain relief. Furthermore, if low elagolix doses are used, ovulation is not consistently inhibited, and patients should use non-hormonal contraceptive systems and perform serial urine pregnancy tests to rule out unplanned conception during periods of treatment-induced amenorrhoea. If high elagolix doses are used to control severe pain for long periods of time, add-back therapies should be added, similar to that prescribed when using GnRH agonists. To date, the efficacy of elagolix has only been demonstrated in placebo-controlled explanatory trials. Pragmatic trials comparing elagolix with low-dose hormonal contraceptives and progestogens should be planned to verify the magnitude of the incremental benefit, if any, of this GnRH antagonist over currently used standard treatments. The price of elagolix may impact on patient adherence and, hence, on clinical effectiveness. In the USA, the manufacturer AbbVie Inc. priced elagolix (OrilissaTM) at around $10 000 a year, i.e. $845 per month. When faced with unaffordable treatments, some patients may choose to forego care. If national healthcare systems are funded by the tax payer, the approval and the use of a new costly drug to treat a chronic condition, such as endometriosis, means that some finite financial resources will be diverted from other areas, or that similar patients will not receive the same level of care. Thus, defining the overall 'value' of a new drug for endometriosis also has ethical implications, and trade-offs between health outcomes and costs should be carefully weighed up.
Several pathogenetic mechanisms have been postulated to explain the association between endometriosis and subfertility. However, to date, definitive conclusions cannot be drawn. In this study, we ...hypothesized that the reduced exploitation of the natural chances of conception could be an additional detrimental factor. Due to dyspareunia or the need for hormonal treatment to temper pelvic pain, one may expect affected women to exploit less the chances of natural pregnancy. In this cross-sectional study of 292 women undergoing IVF, we investigated the severity of pelvic pain symptoms, the sexual function (using the Female Sexual Function Index FSFI), and the reproductive strategies of women with (n = 62) and without (n = 230) endometriosis. Basal clinical and demographic characteristics did not differ between the two groups. Conversely, all pelvic pain symptom scores were increased in women with endometriosis. Endometriosis patients also showed greater pain at the FSFI, but no other significant differences were detected as regards sexual function. The use of hormonal contraceptive agents did not differ between the study groups. Moreover, questions aimed at disentangle whether affected women exploited less the natural chances of pregnancy did not reveal any significant difference. In conclusion, this study does not support the hypothesis that women with endometriosis exploit less the chances of natural pregnancy, despite the presence of pelvic pain.
Picolinamide–cinchona organocatalysts for the successful enantioselective reduction of ketomines were developed. For the first time, a new type of chiral Lewis base, a cationic species, is reported ...to efficiently organocatalyze the addition of trichlorosilane to imines. Excellent yields with good to high enantioselectivities (up to 91 %) were obtained in the reduction of differently substituted substrates. Noteworthy, remarkably high turnover frequencies for the hydrosilylation of imines were observed; the catalyst of choice proved to be active even at a loading of only 1 mol‐%. The loading was further reduced to 0.5 mol‐%, and for very short reaction times (15 min) very impressive asymmetric catalyst efficiency speed values were reached.
Cinchona derivatives for the successful enantioselective addition of trichlorosilane to ketimines are developed. Excellent yields with good to high enantioselectivities (up to 91 %) are obtained in the reduction of differently substituted substrates. Remarkably high turnover frequencies for imine hydrosilylation are observed at a catalyst loading of only 1 mol‐%.
The impact of IVF on deep invasive endometriosis Berlanda, Nicola; Benaglia, Laura; Bottelli, Lara ...
European journal of obstetrics & gynecology and reproductive biology: X,
10/2019, Letnik:
4
Journal Article
Recenzirano
Odprti dostop
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.
Women with endometriosis who underwent IVF and who had a second evaluation after 3-6 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.
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%-5.5%) for the whole cohort and 1.7% (95%CI: 0.08-7.6%) 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.
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.
Levothyroxine has been shown to enhance pregnancy outcomes in women with hypothyroidism requiring in vitro fertilization (IVF). However, the precise magnitude of these benefits remains to be ...determined. In particular, it has yet to be clarified whether levothyroxine may fully overcome the detrimental effects of hypothyroidism or, conversely, whether affected women remain at reduced prognosis for pregnancy outcomes.
Patients who underwent IVF-intracytoplasmic sperm injection (ICSI) over a 3-year period were reviewed. Cases were deemed eligible if they were diagnosed with clinical or subclinical hypothyroidism and were receiving levothyroxine. Controls were two subsequently age-matched euthyroid women for every case. Both cases and controls were selected only if serum thyrotropin was ≤2.5 mIU/L.
In total, 137 women with treated hypothyroidism and 274 controls were included. Baseline characteristics of the two study groups were similar with the exception of body mass index, which was slightly higher among the cases (22.9±3.9 vs. 21.9±3.3 kg/m2, p=0.013). Most IVF-ICSI cycle outcome variables were also similar, with the exception of a higher rate of cancellation for poor response (3.6% vs. 0.7%, p=0.04), a longer duration of stimulation (10.9±2.2 vs. 10.1±2.0 days, p=0.001), a higher proportion of women failing to obtain viable embryos (17% vs. 7%, p=0.006), and a lower fertilization rate (75% vs. 86%, p=0.017) among cases. Conversely, the clinical pregnancy rate per started cycle, the implantation rate, and the live birth rate per started cycle did not differ; they were 36% and 34% (p=0.93), 28% and 22% (p=0.11), and 30% and 27% (p=0.50) in cases and controls, respectively. Subgroup analyses comparing women with (n=79) and without (n=58) thyroid autoimmunity and comparing women who were diagnosed with overt hypothyroidism (n=70) or subclinical hypothyroidism (n=67) failed to identify relevant differences.
In our population, IVF-ICSI outcome was not significantly hampered in women with adequately treated hypothyroidism. The magnitude of the detected differences in cycle outcome was mild, and we failed to document any differences for the most relevant outcomes, i.e., pregnancy rate, implantation rate, and delivery rate. In conclusion, adequate levothyroxine treatment maintaining thyrotropin serum levels below 2.5 mIU/L may overcome the detrimental effects of hypothyroidism.
Abstract Objective To evaluate the rate of euthyroid women encountering an elevation of serum TSH above the threshold of 2.5 mIU/L during controlled ovarian hyperstimulation (COH) for IVF. Study ...design Six-month prospective cohort study on 175 consecutive euthyroid women undergoing their first IVF cycle. Serum TSH assessments were performed before COH, at the time of hCG administration and at +16 days after hCG administration. Women were eligible if serum TSH tested the month preceding the IVF cycle was 0.4–2.5 mIU/L. A history of thyroid disorders was an exclusion criterion. Results Serum concentrations of TSH at the three scheduled assessments were 1.5 ± 0.5, 2.2 ± 1.0 and 2.1 ± 1.1 mIU/L, respectively. A statistically significant increase occurred between basal levels and levels at the time of hCG administration ( p < 0.001). Afterwards, levels remained stable ( p = 0.49). Serum TSH at the time of hCG administration exceeded the threshold of 2.5 mIU/L in 61 subjects, corresponding to 35% (95%CI: 28–42%). At +16 days after hCG administration, this event was observed in 47 subjects (27%, 95%CI: 21–34%). Baseline characteristics of women who did and did not exceed the threshold were similar apart from basal serum TSH, which was higher in the former group. The OR was 7.6 (95%CI: 2.9–20.2) per mIU/L ( p < 0.001). Cycle outcome and pregnancy rate were also similar. Conclusion Serum TSH exceeds the threshold of 2.5 mIU/L during COH in one out of three women who are euthyroid prior to enter an IVF cycle. Further evidence is warranted to elucidate the clinical relevance of our findings.
Having the edge on aromatic–aromatic interactions: Model systems containing aromatic, fluoroaromatic, and heteroaromatic residues arranged in an edge‐to‐face disposition have been synthesized (see ...figure). Investigation of their structures and stereodynamic behavior shows a favorable interaction between an “edge” ring featuring a pyridine nitrogen lone pair and a perfluorinated “face” ring.
Simple model systems based on the 3,3metaparacyclophane skeleton have been designed to study the effect of fluorination of the “face” ring on the edge‐to–face (EtF) interactions with the CArH bond of a phenyl ring or the nitrogen lone‐pair of pyridine. Calculations established that in their more stable conformation the model systems adopt a tilted EtF disposition with the rim of the meta‐substituted ring pointing towards the face of the para‐substituted ring. Topomerization occurs by flipping of the meta‐substituted ring, a process that involves the formation of an intermediate featuring an orthogonal EtF disposition of the arenes, which is less stable than the tilted arrangement. The energy barriers to the isomerization were determined by variable‐temperature NMR spectroscopy and were well reproduced by DFT calculations. The variation in the energy barrier as a function of the substitution of the para‐substituted ring could be rationalized well by a polar interpretation of the EtF interaction in the cases of model systems presenting the PyN̈⋅⋅⋅π interaction but not in the cases of models featuring the CArH⋅⋅⋅π interaction.
Having the edge on aromatic–aromatic interactions: Model systems containing aromatic, fluoroaromatic, and heteroaromatic residues arranged in an edge‐to‐face disposition have been synthesized (see figure). Investigation of their structures and stereodynamic behavior shows a favorable interaction between an “edge” ring featuring a pyridine nitrogen lone pair and a perfluorinated “face” ring.
Four thiophene‐ and furan‐containing 3.3meta(heterocyclo)paracyclophanes were designed and synthesized to study the intramolecular interaction between standard heteroaromatic rings and tetra‐H‐ or ...tetra‐F‐substituted benzenes. A complete conformational analysis, carried out by DFT calculations and variable‐temperature NMR techniques, showed that, despite their structural similarity, these adducts have different conformational preferences and undergo different types of isomerizations depending on the nature of the heterocycle. The thiophene‐derived adducts adopted a parallel stacked arrangement of the aromatic systems in the ground‐state conformations. Their isomerization pathways involved a thiophene ring‐flip process passing through an edge‐to‐face arranged transition state in which the heterocycle is perpendicular to the benzene platform and its sulfur atom points toward the center of that ring. The threshold energy barrier to the ring‐flip process was higher by 10 kJ mol−1 in the case of the adduct featuring the perfluorinated benzene. This difference was rationalized by assuming that the ground‐state conformations of the H‐ and F‐substituted compounds have different stability. On the contrary, the furan‐derived adducts were shown by calculations and NMR spectroscopy to adopt, in their ground‐state conformations, a perpendicular edge‐to‐face disposition of the rings with the oxygen atom pointing toward the benzene platform. The adoption of this arrangement was confirmed by X‐ray crystallography. In the case of these compounds, the isomerization process involved distortion of the CH2SCH2 bridges connecting the aromatic systems and the adoption of transition‐state geometries for which the rings were arranged in a parallel‐stacked orientation. Once again a very nice agreement was observed between the predicted and the experimentally determined geometries and pathways. In the case of the furan‐containing compounds, the threshold barriers were found to be much lower in energy that those observed for the thiophene derivatives. Remarkably, they were virtually independent of the presence of fluorine atoms on the platform benzene ring.
A dive into an electron sea! Four thiophene‐ and furan‐containing 3.3meta(heterocyclo)paracyclophanes were designed and synthesized to study the intramolecular interaction between standard heteroaromatic rings and tetra‐H‐ or tetra‐F‐substituted benzenes. The furan‐derived adducts were shown by calculations and NMR spectroscopy to adopt a perpendicular edge‐to‐face disposition of the rings with the oxygen atom pointing toward the benzene platform (see figure).
PDF
