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RESEARCH QUESTION: Are authors aware when they have cited a retracted paper in their manuscripts in the medically assisted reproduction (MAR) field? DESIGN: A cross-sectional study based on an online survey was conducted to acquire information on the citation pattern from corresponding authors who had cited a retracted article. A dataset of retracted articles in the MAR field was collected from PubMed and Retraction Watch. A complete list of published articles that cited each retracted article was retrieved. The survey was distributed via e-mail to corresponding authors who had cited a retracted paper in their study. RESULTS: The survey revealed a significant lack of awareness among authors, with 78.7% unaware that they had cited retracted articles. This lack of awareness was attributed to insufficient notification mechanisms within research databases and journals, alongside a reliance on previously stored copies of manuscripts. A notable finding was that reference checks were typically performed by a single author, with no instances of retraction concerns raised during the peer-review process. Only a small fraction (17.8%) of respondents reported verifying retraction notices on both journal websites and scientific databases. CONCLUSIONS: Correcting publications that contain references which are subsequently retracted is significant for systematic reviews, meta-analyses and guidelines. Citations of retracted articles perpetuate erroneous scientific data, but assessing the accuracy of citations requires considerable effort. Proper notification of retraction status and cross-checking of citations can help to prevent errors.
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Over the past decade, significant endeavors have been directed toward establishing an optimal oocyte number to maximize the chances for successful in vitro fertilization outcomes. The effectiveness of assisted reproductive technologies has greatly improved, and more good-quality embryos are being created in each cycle. However, many of these embryos remain unused. Notably, in Europe, approximately one-third of couples did not use their surplus cryopreserved embryos. Surplus embryos pose a challenge for patients and clinics. Embryo disposal practices are not the same all over the continent, with embryo donation and embryo discharge not allowed in several countries. In this scenario, limiting the number of surplus embryos by reducing the number of inseminated oocytes, according to couple clinical history, could be a strategy.
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Criopreservação , Transferência Embrionária , Fertilização in vitro , Técnicas de Reprodução Assistida , Feminino , Humanos , Gravidez , Destinação do Embrião/ética , Transferência Embrionária/métodos , Embrião de Mamíferos , Fertilização in vitro/métodos , Oócitos/crescimento & desenvolvimento , Técnicas de Reprodução Assistida/tendênciasRESUMO
PURPOSE: To assess the developmental competence of oocytes matured following rescue in vitro maturation (IVM). METHODS: PubMed, EmBASE, and SCOPUS were systematically searched for peer-reviewed original papers using relevant keywords and Medical Subject Heading terms. Study quality was assessed using the Newcastle-Ottawa Scale. Odds ratios with a 95% confidence interval were calculated by applying a random effects model. The primary outcomes were fertilization and blastulation rates. Secondary outcomes included abnormal fertilization, cleavage, euploidy, clinical pregnancy, and live-birth rates. RESULT: Twenty-four studies were included in the meta-analysis. The oocytes matured following rescue IVM showed significantly reduced fertilization, cleavage, blastulation, and clinical pregnancy rates compared to sibling in vivo-matured oocytes. No significant differences were found for the euploidy and live-birth rates in euploid blastocyst transfer. In poor responders, a reduced fertilization rate was observed using in vitro-matured GV but not with in vitro-matured MI. A reduced cleavage rate in MI matured overnight compared to < 6 incubation hours was found. CONCLUSION: Our results showed compromised developmental competence in oocytes matured following rescue IVM. However, in poor responders, rescue IVM could maximize the efficiency of the treatment. Notably, our data suggests using in vitro MI matured within 6 incubation hours. CLINICAL TRIAL REGISTRATION NUMBER: CRD42023467232.
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Fertilização in vitro , Técnicas de Maturação in Vitro de Oócitos , Oócitos , Taxa de Gravidez , Humanos , Técnicas de Maturação in Vitro de Oócitos/métodos , Feminino , Oócitos/crescimento & desenvolvimento , Gravidez , Fertilização in vitro/métodos , Transferência Embrionária/métodos , Nascido Vivo/epidemiologia , Desenvolvimento Embrionário , Blastocisto/fisiologiaRESUMO
This response letter answers a query regarding our study on the use of the Midjourney app in aesthetic surgery. The original study questioned the utility of Midjourney in enhancing surgical skills, patient understanding, and communication effectiveness. The response highlights the challenges and potential of AI in medical visualization, advocating for meticulous development and evaluation. It stresses the importance of the scientific community's role in educating the public about the reliability and appropriate use of new technologies to avoid misconceptions and ensure the safe integration of AI in advancing medical fields like aesthetic surgery. The authors advocate for ongoing research and thoughtful application of AI tools, acknowledging both their benefits and limitations in the medical context.Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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BACKGROUNDS: The rapid advancement of generative artificial intelligence (AI) systems, such as Midjourney, has paved the way for their use in medical training, producing computer-generated images. However, despite clear disclosures stating that these images are not intended for medical consultations, their accuracy and realism are yet to be thoroughly examined. METHODS: A series of requests were addressed to the Midjourney AI tool, a renowned generative artificial intelligence application, with a focus on depicting appropriate systemic anatomy and representing aesthetic surgery operations. Subsequently, a blinded panel of four experts, with years of experience in anatomy and aesthetic surgery, assessed the images based on three parameters: accuracy, anatomical correctness, and visual impact. Each parameter was scored on a scale of 1-5. RESULTS: All of images produced by Midjourney exhibited significant inaccuracies and lacked correct anatomical representation. While they displayed high visual impact, their unsuitability for medical training and scientific publications became evident. CONCLUSIONS: The implications of these findings are multifaceted. Primarily, the images' inaccuracies render them ineffective for training, leading to potential misconceptions. Additionally, their lack of anatomical correctness limits their applicability in scientific articles. Although the study focuses on a single AI tool, it underscores the need for collaboration between AI developers and medical professionals. The potential integration of accurate medical databases could refine the precision of such AI tools in the future. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Inteligência Artificial , Cirurgia Plástica , Humanos , Cirurgia Plástica/educação , Cirurgia Plástica/métodosRESUMO
STUDY QUESTION: Is it possible to identify a reliable marker of successful sperm retrieval (+SR) in men with idiopathic non-obstructive azoospermia (iNOA) undergoing microdissection testicular sperm extraction (mTESE)? SUMMARY ANSWER: A higher likelihood of +SR during mTESE is observed in men with iNOA and lower preoperative serum anti-Müllerian hormone (AMH) levels, with good predictive accuracy achieved using an AMH threshold of <4 ng/ml. WHAT IS KNOWN ALREADY: AMH has been previously linked to +SR in men with iNOA undergoing mTESE prior to ART. STUDY DESIGN, SIZE, DURATION: A multi-centre cross-sectional study was carried out with a cohort of 117 men with iNOA undergoing mTESE at three tertiary-referral centres. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from 117 consecutive white-European men with iNOA presenting for primary couple's infertility associated with a pure male factor at three centres were analysed. Descriptive statistics was applied to compare patients with negative (-SR) versus +SR at mTESE. Multivariate logistic regression models were fitted to predict +SR at mTESE, after adjusting for possible confounders. Diagnostic accuracy of the factors associated with +SR was assessed. Decision curve analyses were used to display the clinical benefit. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 60 (51.3%) men had an -SR and 57 (48.7%) had a +SR at mTESE. Patients with +SR had lower levels of baseline AMH (P = 0.005) and higher levels of estradiol (E2) (P = 0.01). At multivariate logistic regression analysis, lower levels of AMH (odds ratio: 0.79; 95% CI: 0.64-0.93, P = 0.03) were associated with +SR at mTESE, after adjusting for possible confounders (e.g. age, mean testicular volume, FSH, and E2). A threshold of AMH <4 ng/ml achieved the highest accuracy for +SR at mTESE, with an AUC of 70.3% (95% CI: 59.8-80.7). Decision curve analysis displayed the net clinical benefit of using an AMH <4 ng/ml threshold. LIMITATIONS, REASONS FOR CAUTION: There is a need for external validation in even larger cohorts, across different centres and ethnicities. Systematic reviews and meta-analysis to provide high level of evidence are lacking in the context of AMH and SR rates in men with iNOA. WIDER IMPLICATIONS OF THE FINDINGS: Current findings suggest that slightly more than one in two men with iNOA had -SR at mTESE. Overall, men with iNOA with lower levels of AMH had a significantly higher percentage of successful SR at surgery. A threshold of <4 ng/ml for circulating AMH ensured satisfactory sensitivity, specificity, and positive predictive values in the context of +SR at mTESE. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by voluntary donations from the Urological Research Institute (URI). All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.
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Azoospermia , Humanos , Masculino , Hormônio Antimülleriano , Estudos Transversais , Estudos Retrospectivos , Sêmen , Recuperação EspermáticaRESUMO
PURPOSE: To evaluate the association between progesterone (P) level on the day of trigger and time to blastulation in IVF cycles. METHODS: This was a retrospective cohort study with autologous IVF cycles performed at our Institution from January 2019 to December 2021. A total of 1109 IVF cycles were included. The primary outcome was to compare time to blastulation in terms of percentage of expanded (grade 3) blastocysts on day 5 according to progesterone level at trigger. RESULTS: A total of 3517 blastocysts were analyzed. After dividing progesterone level in quartiles (Q1, P < 0.50 ng/ml; Q2 0.50 ng/ml ≤ P ≤ 0.78 ng/ml; Q3, 0.79 ng/ml ≤ P ≤ 1.15 ng/ml; Q4, P > 1.15 ng/ml), we observed a delay in blastocyst development according to the increasing level of progesterone at trigger (analysis by rank, P-value = 0.01). After adjusting for confounding factors at the multivariate analysis, the percentage of day 5 blastocysts was reduced for Q3 (- 13.8%, 95% CI from - 20.5 to - 7.0%, p < 0.001) and Q4 (- 7.7%, 95% CI from - 15.5 to 0.0%, p = 0.05) compared to Q1 (reference). CONCLUSIONS: Progesterone levels on day of trigger correlate to the percentage of expanded (grade 3) blastocysts on day 5 and a delayed blastocyst development day 5 is expected for high progesterone levels.
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Transferência Embrionária , Progesterona , Humanos , Gravidez , Feminino , Estudos Retrospectivos , Desenvolvimento Embrionário/genética , Blastocisto , Taxa de GravidezRESUMO
PURPOSE: To evaluate the association between serum progesterone (P) at the day of ovulation trigger and neonatal birthweight in singletons born after frozen-thawed embryo transfer in segmented ART cycles. METHODS: A retrospective multicenter cohort study involving data from patients who achieved uncomplicated pregnancy and term delivery of ART-conceived singleton babies following a segmented GnRH antagonist cycle. The main outcome was birthweight's z-score of the neonate. Univariate and multivariate linear logistic regression analyses were made to investigate the relation of z-score with variables inherent to the patient and to the ovarian stimulation. The variable P per oocyte was created by dividing the value of progesterone at ovulation trigger by the number of oocytes retrieved at oocyte retrieval. RESULTS: A total of 368 patients were included in the analysis. At univariate linear regression, the birthweight z-score of the neonate appeared to be inversely related to both P levels at the ovulation trigger (- 0.101, p = 0.015) and P levels per oocyte at trigger (- 1.417, p = 0.001), while it was directly related to the height of the mother (0.026, p = 0.002) and to the number of previous live births (0.291, p = 0.016). In multivariate analysis, both serum P (- 0.1; p = 0.015) and P per oocyte (- 1.347, p = 0.002) maintained the significant inverse association with birthweight z-score after adjusting for height and parity. CONCLUSIONS: Serum progesterone level on the day of ovulation trigger inversely correlates with normalized birthweight of neonates in segmented GnRH antagonist ART cycles.
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Indução da Ovulação , Progesterona/sangue , Transferência Embrionária , Preservação do Sêmen , Estudos Retrospectivos , Peso ao Nascer , Humanos , Feminino , Gravidez , Adulto , Resultado da Gravidez , Recém-NascidoRESUMO
PURPOSE: The aim of the study was to assess the length of diagnostic delay of symptomatic endometriosis in Italy and analyse the presence of correlations between the socio-demographic status of patients and the clinical characteristics/type of diagnosis. MATERIALS AND METHODS: This multicenter cross-sectional questionnaire-based study was conducted in 10 tertiary Italian referral centres for diagnosis and treatment endometriosis. A total of 689 respondents with histologically proven endometriosis and onset of the disease with pain symptoms completed an on-line self-reported questionnaire written in their own language (World Endometriosis Research Foundation-Endometriosis Phenome and Biobanking Harmonisation Project-Endometriosis Patient Questionnaire-Minimum) evaluating endometriosis related symptoms, family history of endometriosis and chronic pelvic pain, demographic data, as well as medical, reproductive, and obstetric history. RESULTS: The mean diagnostic delay found was of 11.4 years. The mean time (14.8 years) from symptoms onset to diagnosis was significantly longer among patients aged 9-19 vs patients aged 20-30 (mean 6.9 years, p < 0.001) and patients aged 31-45 (mean 2.9, p < 0.001). No significant association were found between a delayed diagnosis and any of the clinically relevant factors such as the number or severity of the reported symptoms, familiarity, hormonal therapy intake or methodology of diagnosis. CONCLUSIONS: The mean diagnostic delay of endometriosis in Italy is about 11 years. The delay can be up to 4 years longer in patients with pain symptoms onset under 20 years. Educating clinicians and patients on pathologic nature of endometriosis related pelvic pain is advisable to reduce waiting time to diagnosis, especially for young women.
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Diagnóstico Tardio , Endometriose , Adolescente , Adulto , Criança , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Estudos Transversais , Diagnóstico Tardio/prevenção & controle , Diagnóstico Tardio/estatística & dados numéricos , Endometriose/complicações , Endometriose/diagnóstico , Itália , Dor Pélvica/etiologia , Inquéritos e Questionários , Centros de Atenção TerciáriaRESUMO
RESEARCH QUESTION: Is postnatal growth of singletons aged 12 months born after vitrified-warmed blastocyst transfer (frozen embryo transfer [FET]) different from children born after fresh blastocyst transfer? DESIGN: A retrospective cohort study conducted at a single university-affiliated obstetrics and fertility centre between 2014 and 2016. Women who underwent fresh transfer or FET at blastocyst stage and obtained a singleton live birth were included. Propensity score inverse probability weighting was used to balance baseline maternal characteristics between fresh and FET cycles. RESULTS: Of the 382 women with singleton live births, 124 underwent a fresh blastocyst transfer and 258 underwent a FET. Significantly higher birth weight and length z-scores were observed after FET (Pâ¯=â¯0.01 and Pâ¯=â¯0.002, respectively) compared with the fresh transfer group. At 12 months of age, the fresh and FET groups showed no significant effect on the weight z-score, but the FET was associated with a higher height z-score (Pâ¯=â¯0.001) compared with fresh blastocyst transfer. The comparison between males and females from the same study group showed higher birth weight z-score for males in the FET group (P < 0.001). During the first 12 months, however, males in the FET group showed a slower growth trajectory in terms of weight (Pâ¯=â¯0.007). CONCLUSIONS: At 12 months of postnatal life, an increased height and sex-dependent differences in growth trajectories were observed in singletons born after FET compared with those born after fresh embryo transfer.
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Transferência Embrionária , Vitrificação , Peso ao Nascer , Blastocisto , Criança , Criopreservação , Feminino , Seguimentos , Humanos , Nascido Vivo , Masculino , Gravidez , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
Aim: To develop a predictive model for ovarian failure (OF) after chemotherapy in young post-pubertal women with cancer. Methods: Retrospective, monocentric cohort study including 348 patients referring to the Oncofertility Unit of San Raffaele Hospital (Milan, Italy) from August 2011 to January 2020. A predictive model was constructed by multivariate logistic regression and receiver operating characteristic analysis. Results: Data about menstrual function resumption were available for 184 patients. The best predictive model for OF was identified by the combination of age; number of chemotherapy lines; vincristine, adriamycin, ifosphamide/adriamycin, ifosphamide; capecitabine; adriamycin, bleomycine, vinblastine, doxorubicin (area under the curve = 0.906; CI 95% 0.858-0.954; p = 0.0001). Conclusions: The model predicts the probability of loss of ovarian function at cancer diagnosis and with every change of treatment.
Chemotherapy can reduce fertility in young women surviving cancer. The effects of chemotherapy on ovarian function range from no damage to several degrees of reduced fertility. In some cases, premature menopause can occur. This variability depends on many different individual and treatment-related factors. In this study, we analyzed the outcomes in terms of menses regularity and fertility of 348 oncological patients receiving counseling on fertility at our unit from August 2011 to January 2020. We developed a predictive model to estimate the risk of premature menopause of each patient, to be used at diagnosis and every time a new treatment must be started. This model includes a combination of patient's age, number of lines of chemotherapeutic treatment, and three chemotherapy schedules commonly used in young patients with cancer. It allows an improved counseling on fertility, and it can aid decision making regarding fertility preservation strategies for each patient.
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Preservação da Fertilidade , Neoplasias , Estudos de Coortes , Doxorrubicina/uso terapêutico , Feminino , Humanos , Neoplasias/complicações , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Chemotherapy negatively affects gonadal function, often resulting in premature ovarian failure (POF) due to ovarian reserve depletion. Mechanisms of gonadotoxicity, such as primordial follicle overactivation and "burnout", remain to be established. Ovarian tissue cryopreservation (OTC) before treatment plays an important role in safeguarding fertility. METHODS: This is a prospective observational study that aims to evaluate the feasibility of OTC after chemotherapeutic treatment initiation. Patients were divided into 2 groups depending on whether they received chemotherapy before the harvesting procedure (Group 1) or not (Group 2). The main outcomes of this study are serum anti-Mullerian hormone (AMH) levels and histological follicular counts on ovarian tissue biopsies. RESULTS: Between 2012 and 2020, 79 patients underwent OTC at our Hospital. Follicular counts from the ovarian biopsies of 30 post-pubertal patients and respective serum AMH levels were included in the analysis. AMH levels did not significantly differ between the 2 groups (P = 0.70) as well as the number of primordial follicles (P = 0.73). Ovarian biopsies of patients from Group 1 showed a higher number of primary follicles (P = 0.04) and atretic follicles (P = 0.05) with respect to Group 2. CONCLUSIONS: In conclusion, OTC appears to be feasible even after the start of chemotherapeutic treatment, since in treated patients, the main ovarian reserve indicators (number of primordial follicles and serum AMH levels) were not significantly reduced compared to untreated patients. The "burnout" theory of chemotherapeutic damage to the ovary seems to be supported by the higher number of primary follicles found in the ovaries of patients who received chemotherapy before OTC.
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Antineoplásicos , Reserva Ovariana , Hormônio Antimülleriano , Antineoplásicos/efeitos adversos , Feminino , Humanos , Folículo Ovariano , Ovário/patologia , Estudos ProspectivosRESUMO
RESEARCH QUESTION: How does use of a levonorgestrel-releasing intrauterine system (LNG-IUS) in infertile women with endometrial hyperplasia without atypia affect endometrial hyperplasia regression and pregnancy rates compared with oral medroxyprogesterone acetate (MPA)? DESIGN: This prospective cohort study included 215 infertile women with an indication for assisted reproductive technology (ART) and a diagnosis of endometrial hyperplasia without atypia. Endometrial hyperplasia was diagnosed by hysteroscopic endometrial biopsy. At the time of first- and second-line treatment, patients were offered therapy with either oral MPA 10 mg daily or LNG-IUS. Follow-up biopsies were scheduled after 90 days' treatment. After endometrial hyperplasia regression, patients were admitted to IVF/intracytoplasmic sperm injection (ICSI) cycles. RESULTS: Baseline characteristics and confounders including age at diagnosis, body mass index and duration of infertility did not differ between LNG-IUS users and control participants and were accounted for using propensity score weighting. Endometrial hyperplasia regression rate at first follow-up was higher in the LNG-IUS group than the oral progestins group (28/28, 100% and 110/187, 58.8%; P < 0.001), while that after second-line treatment was comparable between the two groups (89/91, 97.8% and 122/124, 98.4%; P = 0.22). Clinical pregnancy rate, miscarriage rate and cumulative live birth rate following ART in patients ever receiving LNG-IUS were similar to those of patients receiving only MPA (34% versus 39.5%, 22.6% versus 34.7% and 26.4% versus 25.8%). CONCLUSION: Endometrial hyperplasia regression is greater in women receiving LNG-IUS compared with oral MPA, while live birth rates following ART are comparable between the two groups. The use of LNG-IUS does not jeopardize the chances of pregnancy in women seeking fertility treatment.
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Hiperplasia Endometrial/tratamento farmacológico , Infertilidade Feminina/etiologia , Infertilidade Feminina/terapia , Dispositivos Intrauterinos Medicados , Levanogestrel/administração & dosagem , Acetato de Medroxiprogesterona/administração & dosagem , Aborto Espontâneo/epidemiologia , Adulto , Estudos de Coortes , Hiperplasia Endometrial/complicações , Hiperplasia Endometrial/patologia , Feminino , Humanos , Nascido Vivo , Gravidez , Taxa de Gravidez , Estudos Prospectivos , Técnicas de Reprodução Assistida , Resultado do TratamentoRESUMO
According to a rich body of literature, immune cell dysfunctions, both locally and systemically, and an inflammatory environment characterize all forms of endometriosis. Alterations in transcripts and proteins involved in the recruitment of immune cells, in the interaction between cytokines and their receptors, cellular adhesion and apoptosis have been demonstrated in endometriotic lesions. The objective of this narrative review is to provide an overview of the components and mechanisms at the intersection between inflammation and genetics that may constitute vanguard therapeutic approaches in endometriosis. The GWAS technology and pathway-based analysis highlighted the role of the MAPK and the WNT/ß-catenin cascades in the pathogenesis of endometriosis. These signaling pathways have been suggested to interfere with the disease establishment via several mechanisms, including apoptosis, migration and angiogenesis. Extracellular vesicle-associated molecules may be not only interesting to explain some aspects of endometriosis progression, but they may also serve as therapeutic regimens per se. Immune/inflammatory dysfunctions have always represented attractive therapeutic targets in endometriosis. These would be even more interesting if genetic evidence supported the involvement of functional pathways at the basis of these alterations. Targeting these dysfunctions through next-generation inhibitors can constitute a therapeutic alternative for endometriosis.
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Endometriose/genética , Endometriose/imunologia , Endometriose/metabolismo , Endometriose/terapia , Vesículas Extracelulares/metabolismo , Feminino , Humanos , Inflamação/genética , Inflamação/metabolismo , Sistema de Sinalização das MAP Quinases , Terapia de Alvo Molecular , Via de Sinalização WntRESUMO
Preimplantation genetic testing for aneuploidy (PGT-A) still remains controversial in clinical practice. Recently, the randomized controlled trial, 'Single Embryo TrAnsfeR of Euploid Embryo' (STAR) by Munné and coworkers showed a similar live birth rate per intention to treat in the two study groups (PGT-A and controls). A wrong diagnosis and/or biopsy-related damage to the embryo might underlie these results. To assess the impact of these factors on the efficiency of PGT-A, the live birth rate of 'euploid' embryos transferred in the PGT-A group was compared with its ideal value, namely the live birth rate of embryos with the potential to implant and to give rise to a baby in the control group. This estimate has been derived using the results of the genetic testing reported in the STAR trial. According to this model, the STAR trial has demonstrated that transferring only blastocysts classified as 'euploid' after PGT-A leads to a reduction from 82.2% to 50.0% of the live birth rate for competent embryos, thus supporting the idea that PGT-A is associated with some embryo wastage.
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Diagnóstico Pré-Implantação , Transferência de Embrião Único , Aneuploidia , Blastocisto , Feminino , Testes Genéticos , Humanos , GravidezRESUMO
STUDY QUESTION: Given the relevant role of the extracellular microenvironment in regulating tissue homeostasis, is testicular bacterial microbiome (BM) associated with germ cell aplasia in idiopathic non-obstructive azoospermia (iNOA)? SUMMARY ANSWER: A steady increase of dysbiosis was observed among testis with normal spermatogenesis vs. iNOA with positive sperm retrieval and iNOA with complete germ cell aplasia. WHAT IS KNOWN ALREADY: Tissue-associated BM has been reported to be a biologically important extracellular microenvironment component for numerous body habitats, but not yet for the human testis. STUDY DESIGN, SIZE, DURATION: Cross-sectional study, investigating tissue-associated BM in the testis of (i) five men with iNOA and negative sperm retrieval at microdissection testicular sperm extraction (microTESE); (ii) five men with iNOA and positive sperm retrieval at microTESE; and (iii) five normozoospermic men upon orchiectomy. Every testicular specimen was histologically classified and analyzed in terms of bacterial community. PARTICIPANTS/MATERIALS, SETTING, METHODS: Massive ultra-deep pyrosequencing was applied to investigate testis microbiome. Metagenome was analyzed using Quantitative Insights Into Microbial Ecology (QIIME). Tissue-associated bacterial load was quantified by digital droplet PCR. MAIN RESULTS AND THE ROLE OF CHANCE: Normozoospermic men showed small amounts of bacteria in the testis, with Actinobacteria, Bacteroidetes, Firmicutes Proteobacteria as the dominating phyla; iNOA individuals had increased amounts of bacterial DNA (P = 0.02), associated with decreased taxa richness due to the lack of Bacteroidetes and Proteobacteria (P = 2 × 10-5). Specimens with negative sperm retrieval at microTESE depicted complete germ cell aplasia and a further decrease in terms of Firmicutes and Clostridia (P < 0.05), a complete lack of Peptoniphilus asaccharolyticus, but increased amount of Actinobacteria. LIMITATIONS, REASONS FOR CAUTION: The limited number of specimens analyzed in this preliminary study deserves external validation. The paraneoplastic microenvironment could have an impact on the residential bacterial flora. WIDER IMPLICATION OF THE FINDINGS: Human testicular microenvironment is not microbiologically sterile, containing low amounts of Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria. A dysbiotic bacterial community was associated with iNOA and complete germ cell aplasia. Novel findings on testicular BM could support future translational therapies of male-factor infertility. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by URI-Urological Research Institute free funds. Authors declared no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.
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Azoospermia/complicações , Disbiose/complicações , Microbiota , Testículo/microbiologia , Azoospermia/microbiologia , Azoospermia/patologia , Estudos Transversais , Disbiose/microbiologia , Disbiose/patologia , Humanos , Masculino , Espermatogênese/fisiologia , Testículo/patologiaRESUMO
PURPOSE: To investigate the effect of sperm concentration, motility and advanced paternal age on reproductive outcomes. METHODS: A retrospective analysis of 1266 intracytoplasmic sperm injection (ICSI) cycles between 2013 and 2017. The cohort was divided into four groups according to semen concentration based on the WHO criteria (2010): group A (conc. <1 M/ml), group B (1 ≤ conc. <5 M/ml), group C (5 ≤ conc. < 15 M/ml) and the control group D (conc. ≥15 M/ml). The primary outcome investigated was the blastulation rate. Secondary outcomes were fertilization rate, top quality blastocyst formation rate and ongoing pregnancy rate. RESULTS: After adjustment for maternal age and number of oocytes recovered, a significant difference was observed between group A and group D on the rate of fertilized oocytes [66.7 (40.0-80.0) vs 75.0 (57.1-90.2), adjusted p < 0.001] and the blastocyst formation rate [50.0 (33.3-66.3) vs 55.6 (40.0-75.0), adjusted p < 0.05]. However, the male factor did not affect the top quality blastocyst formation rate nor the ongoing pregnancy rate. Considering the age of the male partner as confounding factor, at the increase of each year of age, a reduction of 0.3% on the fertilization rate was observed but no other outcome was impacted. A negative correlation was also observed between sperm motility and fertilization rate in the group with a motility <5%. CONCLUSION: Male factor infertility and advanced paternal age may compromise fertilization and blastulation rates but not top quality blastocyst formation rate or the establishment of pregnancy in ICSI cycles.
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Desenvolvimento Embrionário , Fertilização in vitro , Infertilidade Masculina/terapia , Idade Paterna , Resultado da Gravidez , Motilidade dos Espermatozoides/fisiologia , Espermatozoides/anormalidades , Adulto , Feminino , Humanos , Infertilidade Masculina/patologia , Masculino , Idade Materna , Oócitos/citologia , Oócitos/fisiologia , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Injeções de Esperma IntracitoplásmicasRESUMO
A cost analysis covering direct healthcare costs relating to IVF freeze-all policy was conducted. Normal- and high- responder patients treated with a freeze-all policy (n = 63) compared with fresh transfer IVF (n = 189) matched by age, body mass index, duration and cause of infertility, predictive factors for IVF (number of oocytes used for fertilization) and study period, according to a 1:3 ratio were included. Total costs per patient (6952 versus 6863) and mean costs per live birth were similar between the freeze-all strategy (13,101, 95% CI 10,686 to 17,041) and fresh transfer IVF (15,279, 95% CI 13,212 to 18,030). A mean per live birth cost-saving of 2178 (95% CI -1810 to 6165) resulted in a freeze-all strategy owing to fewer embryo transfer procedures (1.29 ± 0.5 versus 1.41 ± 0.7); differences were not significant. Sensitivity analysis revealed that the freeze-all strategy remained cost-effective until the live birth rate is either higher or only slightly lower (≥-0.59%) in the freeze-all group compared with fresh cycles. A freeze-all policy does not increase costs compared with fresh transfer, owing to negligible additional expenses, i.e. vitrification, endometrial priming and monitoring, against fewer embryo transfer procedures required to achieve pregnancy.
Assuntos
Criopreservação/economia , Transferência Embrionária/economia , Custos de Cuidados de Saúde , Oócitos/citologia , Adulto , Coeficiente de Natalidade , Blastocisto , Estudos de Casos e Controles , Análise Custo-Benefício , Feminino , Fertilização in vitro/economia , Humanos , Infertilidade/terapia , Itália , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , VitrificaçãoRESUMO
INTRODUCTION: The objective of this study was to assess the effectiveness and potential benefits of the use of long-acting recombinant follicle-stimulating hormone (FSH) in a random-start protocol for fertility preservation in women with cancer. MATERIAL AND METHODS: This is a retrospective before-and-after study performed between February 2013 and December 2015 in women who underwent ovarian hyperstimulation for oocyte cryobanking using a random-start approach. In the first part of the study period, the women were treated with daily recombinant FSH whereas in the second part the stimulation was initiated with long-acting recombinant FSH. The primary aim of the study was to compare the number of oocytes stored in the two study periods. In all, 140 women were ultimately selected. RESULTS: Compared with daily recombinant FSH, the use of the long-acting compound was associated with a reduced number of injections (12.5 ± 3.5 vs. 16.4 ± 0.3; p < 0.001) and a longer duration of stimulation (11.4 ± 1.9 vs. 10.6 ± 1.9, p = 0.01). Conversely, the number of oocytes collected (13.7 ± 9.5 vs. 11.3 ± 7.0, p = 0.10) as well as those cryopreserved (11.0 ± 8.0 vs. 9.5 ± 5.8, p = 0.21) did not differ. CONCLUSIONS: The use of long-acting recombinant FSH in random-start protocols for fertility preservation appears to be a valuable option.
Assuntos
Neoplasias da Mama , Preparações de Ação Retardada/administração & dosagem , Preservação da Fertilidade , Hormônio Foliculoestimulante/administração & dosagem , Neoplasias Ovarianas , Indução da Ovulação , Esquema de Medicação , Feminino , Humanos , Gravidez , Estudos Retrospectivos , Resultado do TratamentoRESUMO
A diagnosis of unexplained infertility is commonly made when clinical investigations fail to identify any obvious barriers to conception. As a consequence, unexplained infertility includes several heterogeneous conditions, one being women with age-related infertility. However, the latter represent a peculiar and different situation. Women with age-related infertility may have a different prognosis and may benefit from different treatments. Unfortunately, since fecundity declines with age, discerning between unexplained infertility and age-related infertility becomes more and more difficult as the woman's age increases. In this opinion, with the use of a mathematical model we show that the rate of false positive diagnoses of unexplained infertility increases rapidly after 35 years of age. Using a threshold of 2 years of unfruitful, regular unprotected intercourse, this rate exceeds 50% in women starting pregnancy seeking after 37 years. The scenario is much worse using a threshold of 1 year. From a clinical perspective, extrapolating results obtained in a population of young women with unexplained infertility to those with age-related infertility is not justified. It is noteworthy that, if Assisted Reproductive Technologies are unable to overcome age-related infertility, the older women erroneously labeled with unexplained infertility may receive inappropriate therapies. These may expose women to unjustified risks and waste financial resources. Unfortunately, the available literature about older women is scanty and does not provide valid evidence. Randomized controlled trials aimed at identifying the most suitable clinical management of older women with a normal infertility work-up are pressingly needed.