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Sperm motility is a crucial factor in male fertility. Photobiomodulation (PBM) has been reported to increase sperm motility, but a consistent approach suitable for identifying standardizable protocols is lacking. We collected asthenozoospermic (n = 70) and normozoospermic (n = 20) semen. The asthenozoospermic samples were irradiated with an 810 nm diode laser, in continuous wave mode, at 0.25 W, 0.5 W, 1 W and 2 W for 60 s on a circular area of 1 cm 2  through a novel handpiece with an innovative flat-top profile. Sperm motility was assessed immediately, after 30 and 60 min. A sample size calculator, unpaired t-test and one-way ANOVA with post-hoc Tukey HSD tests were used for statistics. One and 2 W were the most effective outputs in increasing progressive motility compared to control (p < 0.001). The maximum effect was immediately after 1 W-PBM (p < 0.001) and decreased after 60 min (p < 0.001). Time physiologically decreased vitality (p < 0.001), but less in the 1 W-PBM samples (p < 0.05). 1 W-PBM did not affect chromatin condensation. Asthenozoospermic samples displayed an impairment of 80% in oxygen consumption and ATP production and a slight inefficiency of oxidative phosphorylation compared to normozoospermic samples (p < 0.001). 1 W-PBM partially restored the functionality of aerobic metabolism (p < 0.001) by recovery of oxidative phosphorylation efficiency. PBM did not affect lactate dehydrogenase (glycolysis pathway). No irradiated samples increased accumulated malondialdehyde, a marker of lipidic peroxidation. In conclusion, PBM improves progressive motility in asthenozoospermia through increased mitochondrial energetic metabolism without harmful oxidative stress., (© 2024. The Author(s).)

Objectives: To compare menopausal symptoms of breast cancer survivors on adjuvant endocrine therapy with those of menopausal women., Study Design: In a retrospective nested case-control study menopausal symptoms were compared of breast cancer survivors in pre-, peri- or post-menopause at the time of diagnosis, on tamoxifen or an aromatase inhibitor, plus a gonadotrophin-releasing hormone analogue, if pre- or peri-menopausal, and age-matched control women either in the late peri-menopause, or in surgical or in physiological post-menopause on no hormone replacement therapy. Differences between women on tamoxifen and those on aromatase inhibitors were also evaluated. Weighted and non-weighted t-tests, chi-square tests, and linear or logistic regressions were applied as appropriate., Main Outcome Measures: Score on the Greene's Climacteric Scale and so of its subscales evaluating vasomotor, anxiety, depression, somatisation and sexuality symptoms., Results: A total of 99 breast cancer survivors (45 on tamoxifen, 54 on aromatase inhibitors) and 554 controls (173 in late perimenopause, 353 in natural and 28 in surgical menopause) were enrolled. The score on the Greene's Climacteric Scale was similar in cases and controls (means ± standard deviation) (21.3 ± 10.4 vs. 22.8 ± 11.5, p = 0.199), as were the subscale scores for vasomotor symptoms, anxiety, and somatisation. The depression score was lower (4.63 ± 3.3 vs. 5.98 ± 3.8; p = 0.001) in breast cancer survivors on adjuvant endocrine therapy, mainly due to a lower score of -2.132 (95 % confidence interval - 3.858/-0.407; p = 0.016) for users of aromatase inhibitors. The sexuality score was higher (1.76 ± 1.1 vs. 1.50 ± 1.1, p = 0.011) than in controls. Differences remained significant when corrected for age, menarche, body mass index, menopausal status (peri- or post-), type of menopause (natural, surgical), use of gonadotrophin-releasing hormone analogues, years of amenorrhea, smoking, alcohol use, and for breast radiotherapy, chemotherapy, tamoxifen or aromatase inhibitors. Among breast cancer survivors, women on aromatase inhibitors had lower scores for anxiety (5.75 ± 2.5vs.5.75 ± 2.5; p = 0.045) and depression (3.89 ± 2.5 vs. 5.13 ± 3.6; p = 0.046) than women on tamoxifen., Conclusions: In breast cancer survivors, adjuvant therapy induces symptoms similar in type and intensity to those of symptomatic menopausal women. Compared with menopausal women, breast cancer survivors, particularly those on aromatase inhibitors, appear to experience less severe depressive symptoms., Competing Interests: Declaration of competing interest M. Lambertini reports advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences; speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Takeda, Gilead; travel Grants from Gilead, Daiichi Sankyo, Roche; research funding (to the Institution) from Gilead all outside the submitted work. Prof. Lucia L. Del Mastro reports advisory role and/or speaker honoraria for Roche, Eli Lilly, Novartis, Pfizer, Pierre Fabre, Eisai, Gilead, Astrazeneca, Daiichi Sankyio, Gilead, Exact sciences, Agendia, Menarini Stemline, Olema, Ipsen, MSD; travel grants from Gilead, daiichi Sankyo, Astrazeneca, Roche; research funding (to the institution) from Pfizer, all outside the submitted work. The other authors declare no conflict of interest with the content of the present article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Denosumab is a monoclonal anti-RANKL antibody that inhibits bone resorption, increases bone mass, and reduces fracture risk. Denosumab discontinuation causes an extensive wave of rebound resorption, but the cellular mechanisms remain poorly characterized. We utilized in situ hybridization (ISH) as a direct approach to identify the cells that activate osteoclastogenesis through the RANKL/OPG pathway. ISH was performed across species, skeletal sites, and following recombinant OPG (OPG:Fc) and parathyroid hormone 1-34 (PTH) treatment of mice. OPG:Fc treatment in mice induced an increased expression of RANKL mRNA mainly in trabecular, but not endocortical bone surface cells. Additionally, a decreased expression of OPG mRNA was detected in bone surface cells and osteocytes of both compartments. A similar but more pronounced effect on RANKL and OPG expression was seen one hour after PTH treatment. These findings suggest that bone surface cells and osteocytes conjointly regulate the activation of osteoclastogenesis, and that OPG:Fc treatment induces a local accumulation of osteoclastogenic activation sites, ready to recruit and activate osteoclasts upon treatment discontinuation. Analysis of publicly available single-cell RNA sequencing (scRNAseq) data from murine bone marrow stromal cells revealed that Tnfsf11 + cells expressed high levels of Mmp13, Limch1, and Wif1, confirming their osteoprogenitor status. ISH confirmed co-expression of Mmp13 and Tnfsf11 in bone surface cells of both vehicle- and OPG:Fc-treated mice. Under physiological conditions of human/mouse bone, RANKL is expressed mainly by osteoprogenitors proximate to the osteoclasts, while OPG is expressed mainly by osteocytes and bone-forming osteoblasts., (© 2024. The Author(s).)

Introduction: Breast cancer is the most common malignancy in women of reproductive age and chemotherapy protocols impair fertility, frequently necessitating fertility preservation (FP) referral. Embryo, oocyte, or ovarian tissue cryopreservation are established FP modalities in women with breast cancer but there are few data on their uptake over time. In this study our aim was to determine the regional time trends and utility differences for fertility preservation methods of reproductive tissue cryopreservation., Methods: This multicenter study included 1623 women diagnosed with breast cancer from 7 tertiary centers in 6 countries (Brazil, Italy, Scotland, South Korea, Turkey, USA). Participant centers provided the details of FP cryopreservation approaches broken down annually from 2012 to 2021. Women with newly diagnosed breast cancer, aged 18-45 years who were referred for FP at participating centers and had normal ovarian function at the time were included., Results: We found a mean increase of 7% per year (P = .002, adjusting for centers) in the number of women referred for FP. Of those who were referred (n = 1623), a mean 38.7% underwent FP (n = 629), with a range of 12% in South Korea) to 95% in Brazil. The number of women undergoing ovarian stimulation for FP continually increased until 2021, with oocyte cryopreservation being the most common procedure throughout the study period (P = .014 for time trend). The proportion of random start ovarian stimulation cycles increased each year from 58.3% in 2012 to 86.8% in 2021, (P = .005 for time trend, and P = .04 for 2012 vs. 2021)., Conclusions: The utility of FP has steadily increased for young women with breast cancer over the last decade, although regional differences significantly influence FP practices. The findings of our study could have value for policy making in FP care for young women with breast cancer at the local, regional, or global level., Competing Interests: Disclosure Dr. Lambertini reports advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, MSD, and Exact Sciences; speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Takeda, Knight, Ipsen, and AstraZeneca; travel Grants from Gilead, Daiichi Sankyo, Roche and a research grant (to his Institution) from Gilead, all outside the submitted work. All other authors state that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Cryopreservation of human spermatozoa is a widely used technique in the assisted reproduction technology laboratory for the storage of gametes for later use, for the fertility preservation and for sperm donation programs. Cryopreservation can cause damage to membrane, cytoskeletal, acrosome and increased oxidative stress, sperm DNA damage and transcriptome changes. To assess the impact of storage time on the transcriptome of frozen human spermatozoa, semen samples were collected from 24 normospermic donors of whom 13 had cryostored semen for a short-time (1 week) and 11 had cryostored semen for a long-time (median 9 years)., Results: RNA was extracted from each frozen-thawed sperm sample, randomized in pools, and analyzed by microarrays. Five transcripts were in higher abundance in the long-time respect to the short-time storage group. Functional annotation enrichment disclosed that that the length of cryostorage has no effect on critical pathways involved in sperm physiology and function., Conclusions: The storage time of cryopreserved human spermatozoa does not affect pathways involved in fertility., (© 2024. The Author(s).)

Purpose: This position statement by the Italian Society of Fertility and Sterility and Reproductive Medicine (SIFES-MR) aims to establish an optimal framework for fertility preservation outside the standard before oncological therapies. Key topics include the role of fertility units in comprehensive fertility assessment, factors impacting ovarian potential, available preservation methods, and appropriate criteria for offering such interventions., Methods: The SIFES-MR writing group comprises Italian reproductive physicians, embryologists, and scientists. The consensus emerged after a six-month period of meetings, including extensive literature review, dialogue among authors and input from society members. Final approval was granted by the SIFES-MR governing council., Results: Fertility counselling transitions from urgent to long-term care, emphasizing family planning. Age, along with ovarian reserve markers, is the primary predictor of female fertility. Various factors, including gynecological conditions, autoimmune disorders, and prior gonadotoxic therapies, may impact ovarian reserve. Oocyte cryopreservation should be the preferred method. Women 30-34 years old and 35-39 years old, without known pathologies impacting the ovarian reserve, should cryopreserve at least 12-13 and 15-20 oocytes to achieve the same chance of a spontaneous live birth they would have if they tried to conceive at the age of cryopreservation (63% and 52%, respectively in the two age groups)., Conclusions: Optimal fertility counselling necessitates a long-term approach, that nurtures an understanding of fertility, facilitates timely evaluation of factors that may affect fertility, and explores fertility preservation choices at opportune intervals., (© 2024. The Author(s).)

Approximately 10% to 15% of breast cancer cases in young women are diagnosed in patients harbouring germline (g) pathogenic or likely pathogenic variants (PVs) in the BReast CAncer 1 ( BRCA1 ) or BReast CAncer 2 ( BRCA2 ) genes. Preclinical and clinical studies showed a potential negative effect of germline BRCA 1/2 (g BRCA1/2 ) PVs on ovarian reserve and reproductive potential, even before starting anticancer therapies. The aim of this article is to summarize the current literature on the fertility potential of young g BRCA1/2 PVs carriers with breast cancer and the risk of gonadotoxicity associated with anticancer treatments. Moreover, we describe the available evidence on the efficacy of fertility preservation techniques in young g BRCA1/2 PVs carriers and the safety data on having a pregnancy after breast cancer treatment., (© The Author(s) 2024.)

Sperm cryopreservation is a procedure widely used to store gametes for later use, to preserve fertility in patients prior to gonadotoxic treatments or surgery, and for sperm donation programs. The purpose of the study was to assess the impact of cryopreservation on human sperm transcriptome. Semen samples were collected from 13 normospermic men. Each sample was divided into two aliquots. The total RNA was immediately extracted from one aliquot. The second aliquot was frozen and total RNA was extracted after a week of storage in liquid nitrogen. The RNA samples were randomized in four pools, each of six donors, and analyzed by microarrays. The paired Significance Analysis of Microarray was performed. We found 219 lower abundant transcripts and 28 higher abundant transcripts in cryopreserved sperm than fresh sperm. The gene ontology analysis disclosed that cryopreservation alters transcripts of pathways important for fertility (i.e., spermatogenesis, sperm motility, mitochondria function, fertilization, calcium homeostasis, cell differentiation, and early embryo development), although the increase of some transcripts involved in immune response can compensate for the harmful effects of freezing., Competing Interests: M.L. reports advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, MSD, and Exact Sciences and speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Knight, and Takeda, Travel Grants from Gilead and Daiichi Sankyo, and research support (to the Institution) from Gilead outside the submitted work. P.A. reports speaker honoraria from Gedeon Richter, Merck, and Organon outside the submitted work. The other authors declare no conflicts of interest.

In the registrational trials, follitropin delta was compared with a fixed dose of 150 UI of follitropin alpha/beta, finding higher chances to reach a target response of 8-14 oocytes compared to controls. For this reason, follitropin delta is marketed as particularly useful in expected hyper-responder patients. The main outcome of this study is to report if comparable results are reached in a real-life scenario with follitropin alpha/beta personalized doses, based on patients' characteristics. This is a retrospective study performed in two public fertility centres. All first cycles from January 2020 to June 2022 with either follitropin delta (cases) or alpha/beta (controls) in patients with antiMüllerian hormone >2.5 ng/ml were compared by an inverse probability weighting approach based on propensity score. The follitropin total dose was higher in controls (1179.06 ± 344.93 vs. 1668.67 ± 555.22 IU, p<0.001). The target response of 8-14 oocytes was reached by 40.2% of cases and 40.7% of controls (odds ratio (OR) 0.99, 95% confidence interval (CI) 0.65-1.53, p=0.98). Fewer than 8 oocytes were collected in 24.1% of cases and 22% of controls (OR 1.10, 95% CI 0.71-1.69, p=0.67); more than 14 oocytes in 35.7% of cases and 37.3% of controls (OR 0.83, 95% CI 0.54-1.28, p=0.40). Our experience did not find worse results in term of proportion of patients who reached the target response with an algorithm-chosen dose of follitropin delta compared to a personalised starting dose of follitropin alpha/beta, with follitropin delta having the advantage of objectivity. Larger numbers are needed to confirm these results.

Background: In fertility clinics the standard approach to semen collection involves a private room close to the laboratory to avoid fluctuations in temperature and to control the time between collection and processing. There are still no firm conclusions whether collecting semen at home has any influence on sperm quality and reproductive competence. The purpose of this study was to assess whether the site of semen collection affects semen parameters., Methods: This retrospective cohort study performed at a tertiary level public fertility center included 8634 semen samples from 5880 men undergoing fertility assessment from 2015 to 2021. The impact of sample collection site was evaluated using a generalized linear mixed model. A subgroup analysis comparing clinic to home collection within the same patient was performed on 1260 samples from 428 men by paired t-test or Wilcoxon Signed Rank Test., Results: Samples collected at home (N.=3240) had significantly higher semen volume, sperm concentration and total sperm count respect to samples collected at clinic (N.=5530) (median (range): 2.9 (0.0-13.9) mL versus 2.9 (0.0-11.5) mL, P=0.016; 24.0 (0.0-252.0) million/mL versus 18.0 (0.0-390.0), P<0.0001; 64.6 (0.0-946.0) million versus 49.3 (0.0-1045.0), P<0.0001, respectively). There was no difference in abstinence period and sperm motility. Paired comparisons of semen characteristics in 428 patients with home-collected (N.=583) and clinic-collected (N.=677) samples confirmed a no negative effect on volume and total sperm count., Conclusions: Our data provide evidence for a not disadvantage with collection at home.

Background: In Italy during the first pandemic wave of SARS-CoV-2 the activity of fertility centers was stopped, with the exception of fertility preservation in oncological patients. We adopted telehealth and we evaluated whether it could help in the management of infertile couples at a fertility center., Methods: A longitudinal study performed at a public fertility center. Telehealth was offered to 72 couples referred to our center for a first consultation from March 17 th to May 31 st , 2020. Percentage of patients who performed the first assisted reproduction technology (ART) cycle or intrauterine insemination (IUI) within 6 months from the first visit and drop-out rate were analyzed during COVID-19 pandemic and compared to historical controls (couples admitted to our center in 2017-2019)., Results: Eighty-five (61/72) percent of the couples accepted telehealth. Time to first treatment after online consultation in telehealth group (4.5±1.8 months) was significantly shorter (P=0.033) respect to time to first treatment after face-to-face visit of historical controls (7.5±6.9 months). After telehealth consultation, we observed a significant reduction (P=0.002) of drop-out rate from 39% in historical controls to 17% of telehealth group. Telehealth significantly diminished the drop-out rate also during the COVID-19 pandemic respect to 73% after traditional face-to-face visits (P=0.0005), with a time to first treatment of 3.7±2.1 months in couples who refused telehealth., Conclusions: Telehealth could be a useful tool to facilitate the path of patients in a fertility center.

Objective: This study aims to assess the factors associated with the success and failure rate of the external cephalic version (ECV) in breech fetuses. Secondary outcomes were fetal presentation in labor and mode of delivery., Methods: This cross-sectional study examined the live birth certificates from 2003 through 2020 from US states and territories that implemented the 2003 revision. A total of 149,671 singleton pregnancies with information about ECV success or failure were included. The outcome was ECV success/failure, while the exposures were possible factors associated with the outcome., Results: The successful ECV procedures were 96,137 (64.23%). Among the successful ECV procedures, the prevalence of spontaneous vaginal delivery was 71.63%. Among the failed ECV procedures, 24.74% had a cephalic presentation at delivery, but 63.11% of these pregnancies were delivered by cesarean section. Nulliparity, female sex, low fetal weight centile, high pre-pregnancy BMI, high BMI at delivery, and high maternal weight gain during pregnancy were associated with an increased ECV failure (p < 0.001). African American, American Indian and Alaska Native race categories were significant protective factors against ECV failure (p < 0.001). Maternal age had a U-shape risk profile, whereas younger maternal age (< 25 years) and old maternal age (> 40 years) were significant protective factors against ECV failure (p < 0.001)., Conclusions: A high prevalence of successful ECV procedures and subsequent spontaneous vaginal delivery were found. The present results found nulliparity, maternal race, maternal age, female fetal sex, low fetal weight, and maternal anthropometric features correlated to ECV results. These findings can potentially improve the knowledge about the factors involved in ECV, allowing more informed counseling to the women undergoing this procedure., (© 2022. The Author(s).)

Since essential factors have changed in recent years in assisted reproduction technologies (ARTs), this study reassessed the association between ART and breech presentation. We primarily aimed to estimate the correlation between ART and breech at delivery. Secondary purposes were to evaluate the correlation between other subfertility treatments (OSTs) and breech and to assess possible confounding factors and temporal trends. This study investigated the 31,692,729 live birth certificates from US states and territories in the 2009-2020 period. The inclusion criteria were singleton births reporting the method of conception and the presentation at delivery. The outcome was the breech presentation at delivery, while the primary exposure was ART, the secondary exposure was OST, and the potential confounding factors from the literature were considered. ART (OR 2.32 CI.95 2.23-2.41) and OST (OR 1.79 CI.95 1.71-1.87) were independent and significant risk factors for breech at delivery ( p < 0.001). This study confirmed breech presentation risk factors maternal age, nulliparity, tobacco smoke, a previous cesarean delivery (CD), neonatal female sex, gestational age, and birth weight. Black race and Hispanic origin were verified to be protective factors. We found breech prevalence among ART and OST to be stable during the study period. Meanwhile, newborn birth weight was increased, and the gap between breech and other presentations in ART was reduced. Our results indicate that singleton pregnancies conceived by ART or OST were associated with a higher risk of breech at delivery. Well-known risk factors for the breech presentation were also confirmed. Some of these factors can be modified by implementing interventions to reduce their prevalence (e.g., tobacco smoke and previous CD).