A Pilot Analysis of Whole Transcriptome of Human Cryopreserved Sperm.

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.

Oxidative Stress: The Role of Estrogen and Progesterone.

The effect of estrogen and progesterone on oxidative status is not yet very clear, improvements and detrimental effects having been reported with the use of menopausal hormone therapy or hormonal contraceptives, respectively. In this study, we evaluated the role played by estrogen and progesterone separately, on the oxidative status of 32 women, 18 to 43 years old, by inducing high levels of estrogen and then adding high levels of progesterone. During a cycle of in vitro fertilization, blood samples were collected prior to gonadotrophin stimulation (low estradiol levels), on the day of oocyte retrieval (high levels of estrogen), and on the day of embryo transfer (high levels of estrogen and progesterone). Total blood levels of oxidants (FORT), antioxidants (FORD), and their ratio FORT/FORD were measured using a colorimetric method based on the Fenton reaction. Seven women measured their early morning body temperature at the same time points. FORT significantly decreased from the low- to the high-estrogen phase (p = 0.023) and increased from the high-estrogen to the high-estrogen-progesterone phase (p = 0.006). FORD showed an opposite but non-significant trend. The FORT/FORD ratio decreased from the low- to the high-estrogen phase (p = 0.0104) and increased from the high-estrogen to the high-estrogen -progesterone phase (p = 0.004). Body temperature (n = 7) decreased in the high-estrogen phase (p = 0.001) and increased from the high-estrogen to the high-estrogen-progesterone phase (p = 0.001). In the seven women, FORT (p = 0.009) and FORT/FORD (p = 0.0056) were linearly related to body temperature values. Our data show opposite effects of estrogen and progesterone on oxidative status. These effects seem to be related to the effect exerted on body temperature regulation.

The Role of Cyclin-Dependent Kinases (CDK) 4/6 in the Ovarian Tissue and the Possible Effects of Their Exogenous Inhibition.

The combination of cyclin-dependent kinase (CDK) 4/6 inhibitors with endocrine therapy is the standard treatment for patients with HR+/HER2- advanced breast cancer. Recently, this combination has also entered the early setting as an adjuvant treatment in patients with HR+/HER2- disease at a high risk of disease recurrence following (neo)adjuvant chemotherapy. Despite their current use in clinical practice, limited data on the potential gonadotoxicity of CDK4/6 inhibitors are available. Hence, fully informed treatment decision making by premenopausal patients concerned about the potential development of premature ovarian insufficiency and infertility with the proposed therapy remains difficult. The cell cycle progression of granulosa and cumulus cells is a critical process for ovarian function, especially for ensuring proper follicular growth and acquiring competence. Due to the pharmacological properties of CDK4/6 inhibitors, there could be a potentially negative impact on ovarian function and fertility in women of reproductive age. This review aims to summarize the role of the cyclin D-CDK4 and CDK6 complexes in the ovary and the potential impact of CDK4/6 inhibition on its physiological processes.

Does SARS-CoV-2 Affect the Prostate? A Molecular Analysis from a Case Series of COVID-19 Patients.

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) causes COVID-19 that has been spreading worldwide since December 2019. Viral entry into cells requires expression of both angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) on the surface of the host cell. The male reproductive system, including the prostate, was supposed to be a potential target for SARS-CoV-2 since the presence of ACE and TMPRS2 receptors. This paper investigated for the first time the presence of SARS-CoV-2 mRNA in the prostatic tissue of a patient with active infection. In addition, we searched for the virus in the prostate of five patients after their recovery from COVID-19. The SARS-CoV-2 RNA was not detected in any of the prostate tissues tested even during the acute phase of infection. As case series have limitations, causality cannot be excluded and sporadic evidence of prostatic tissue invasion by SARS-CoV-2 may be detectable.

Collecting semen samples at home for fertility assessment: time for a new standard?

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.

Telehealth for infertile patients during SARS-CoV-2 pandemic: far, and yet close.

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 17th to May 31st, 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.

mRNA and Viral Vector COVID-19 Vaccines Do Not Affect Male Fertility: A Prospective Study.

PURPOSE: To assess whether mRNA and viral vector coronavirus disease 2019 (COVID-19) vaccines detrimentally affected semen parameters. MATERIALS AND METHODS: In this prospective study, we enrolled 101 men vaccinated for COVID-19 (76% received mRNA vaccines, 20% viral vector vaccines, 2% a mixed formulation, and for 2 men no information about vaccine type was available) in 2021 and with a previous semen analysis. For each man we compared semen parameters before and after vaccination. RESULTS: Post-vaccine samples were obtained at a median of 2.3±1.5 months after the second dose. After vaccination, the median sample volume significantly decreased (from 3.0 to 2.6 mL, p=0.036), whereas the median sperm concentration, the progressive motility, and total motile sperm count increased (from 25.0 to 43.0 million/mL, p<0.0001; from 50% to 56%, p=0.022; from 34.8 to 54.6 million, p<0.0001, respectively). Thirty-four patients were oligospermic before the vaccine, and also in these patients we observed a significant increase of sperm parameters after vaccine. Finally, we confirmed the aforementioned results in men who received a mRNA or a viral vector vaccine. CONCLUSIONS: The semen parameters following COVID-19 vaccination did not reflect any causative detrimental effect from vaccination, and for the first time we demonstrated that this applies to both mRNA and viral-vector vaccines. The known individual variation in semen and the reduced abstinence time before the post-vaccine sample collection may explain the increases in sperm parameters.

Hyaluronic acid-sperm selection significantly improves the clinical outcome of couples with previous ICSI cycles failure.

BACKGROUND: Beneficial effects of hyaluronic acid (HA)-based selection of spermatozoa for intracytoplasmic sperm injection (ICSI) are still controversial, and further studies are needed to categorize patients that might benefit from such a method. OBJECTIVE: We investigated whether HA sperm selection improved ICSI outcome of couples with previous ICSI cycle failure. MATERIALS AND METHODS: In this retrospective study, we prospectively collected data of (i) Group 1: 96 couples who performed one failed ICSI cycle ("1st procedure," n = 96) followed by another ICSI cycle ("2nd procedure," n = 101); ii) Group 2: 87 couples who performed one failed ICSI cycle (n = 87) followed by an HA-ICSI cycle (n = 104). Differences between procedures and groups were measured by paired and independent statistical tests, respectively. A generalized linear mixed model analyzed the effect of procedure on the outcomes and the interaction between procedures and groups. RESULTS: Injection of HA-bound sperm significantly improved cleavage rate with respect to standard ICSI (p = 0.026). No evolutive pregnancies were obtained in the 1st ICSI attempts. The 2nd ICSI cycles resulted in successfully seven pregnancies. In HA-ICSI cycles, the better quality of embryos with respect to ICSI (p = 0.034) increased the choice of day 5 embryo transfer (p = 0.030), which resulted in successfully 28 pregnancies. No differences were observed in clinical outcomes of the two ICSI procedures in Group 1, while pregnancy and implantation rates were significantly higher in HA-ICSI with respect to ICSI cycles (p = 0.001, p < 0.0001, respectively). No negative perinatal outcomes were recorded. DISCUSSION: In couples where previous 1st ICSI failed, selection of HA-bound spermatozoa significantly improved clinical outcomes with respect to further standard ICSI. CONCLUSION: This study identified couples with previous ICSI cycles failure as a category of infertile patients that really may benefit from HA sperm selection before ICSI.

Semen parameters and male reproductive potential are not adversely affected after three or more months of recovery from COVID-19 disease.

Background: The male reproductive system may be a potential target for SARS-CoV-2 since the presence of ACE and TMPRS2 receptors. After a first report of the presence of SARS-CoV-2 in semen of COVID-19 patients, several papers reported that SARS-CoV-2 was not detected in the semen. However, some evidences indicated that COVID-19 disease could impair semen parameters. During the infection, or in a short period after, a reduction in sperm concentration and motility and an increase in DNA fragmentation were observed, even in asymptomatic patients. There is no conclusive data exploring whether this damage changes with time. We investigated whether COVID-19 disease has a negative impact on semen parameters and male reproductive potential after recovery. Methods: In this longitudinal retrospective study, we enrolled 20 men who had COVID-19 disease. We compared sperm parameters in samples collected before COVID-19 and after infection (8.3 ± 4.8 months). We also evaluated the reproductive potential in pre- and post-COVID-19 infertility treatments of 8 self-controlled couples as well as in 40 cycles after COVID-19 infection of the male partner. Results: For most patients, we obtained results of more than one semen analysis before and after COVID-19. After adjusting for age, days of sexual abstinence, frequency of ejaculations and presence of fever, we found no significant difference over time in any semen parameter. The interval between COVID-19 infection and subsequent infertility treatments was 10.7 ± 7.5 months. There were no differences in the embryological and clinical outcomes of infertility treatments performed before and after male infection. One couple obtained a single pregnancy in the post COVID-19 IUI. Normal fertilization (65%), cleavage (99%) and blastocyst development (40%) rates in treatments performed after male infection were within the expected range of competencies. A total of 5 singleton and 1 twin clinical pregnancies were obtained, and 6 healthy children were born. A total of 10 blastocysts have been cryopreserved. Conclusion: Our data are reassuring that COVID-19 disease has no negative effect on semen quality and male reproductive potential when semen samples are collected three months or more after infection.

Effect of Multiple Sclerosis and Its Treatments on Male Fertility: Cues for Future Research.

Multiple sclerosis is a chronic disease that may lead to different types of symptoms and disabilities. with the better quality of life and decreased disability due to early diagnosis and the availability of disease-modifying therapies (DMTs), the treating physician is increasingly asked to counsel patients on its effects on fertility and reproduction. In particular, reproductive issues are still scarcely studied and discussed in men. Among the still open questions are the following: (a) Does multiple sclerosis cause infertility per sè? (b) Is multiple sclerosis correlated with conditions that increase the risk of infertility? (c) Do DMTs or other therapies for multiple sclerosis impact gonadal function in men? The aim of this review is to provide an overview on the available literature data about the reproductive issues unique to men with multiple sclerosis, underlining the numerous areas where evidence is lacking and, therefore, the priorities for future research.

Oral Antioxidant Treatment of Men Significantly Improves the Reproductive Outcome of IVF Cycles.

Some 30% to 80% of male sub-fertility may be associated with oxidative stress that damages spermatozoa and can decrease success of in vitro fertilization (IVF) techniques. This multicenter, longitudinal, prospective study aimed to investigate whether oral antioxidant supplementation improved the reproductive competence of men who had had low fertilization rates in their previous intracytoplasmic sperm injection (ICSI) cycles without azoospermia or severe oligozoospermia or any identifiable andrological disease. Seventy-seven men from couples who had an ICSI attempt with unexplained <60% fertilization rate took an antioxidant mix of myo-inositol, alpha-lipoic acid, folic acid, coenzyme Q10, zinc, selenium, and vitamins B2, B6, and B12. Semen parameters were analyzed before (T0) and after 90 days (T90) of treatment, and outcomes of the paired T0 and T90 cycles were compared. After the treatment there was an increase in sperm concentration (p = 0.027), total motile sperm count (p = 0.003), progressive motility (p < 0.0001), and a decreasing trend of DNA-fragmented spermatozoa. Embryological outcomes (fertilization, embryo quality, blastocyst development) were significantly higher in T90 than T0 cycles. No T0 cycle resulted in an evolutive pregnancy. Conversely, in T90 cycles 29 singleton clinical pregnancies were obtained. No negative neonatal outcomes were recorded in newborns after antioxidant treatment. Diet supplementation of men who have had low fertilization rates in their previous ICSI cycles with a combination of myo-inositol, alpha-lipoic acid, folic acid, coenzyme Q10, zinc, selenium, betaine, and vitamins may improve semen reproductive potential and ICSI clinical outcome.

Pronuclear score improves prediction of embryo implantation success in ICSI cycles.

BACKGROUND: In assisted reproduction technology embryo competence is routinely evaluated on morphological criteria but efficacy remains relatively low. Additional information could be obtained by evaluating pronuclear (PN) morphology. Up to now controversial results have been reported about the prognostic value of PN score. One of the main limitations of literature data is the use of different PN classification methods. In this regard, in 2011 the ESHRE and Alpha Scientists in Reproductive Medicine defined three PN categories to standardize zygote assessment. In this study we evaluated whether the consensus ESHRE-Alpha system for the pronuclear scoring could be an useful additional criterion to improve prediction of embryo implantation potential. METHODS: This is a retrospective, longitudinal, observational, cohort study. We included 3004 zygotes from 555 women who underwent ICSI treatment at our Center between January 2014 and June 2019. The PN were categorized as score 1: symmetrical, 2: non-symmetrical, 3: abnormal. A subset of 110 zygotes did not cleaved. On day 2-3 1163 embryos were transferred, 232 arrested, and 9 were cryopreserved. Among the 1490 embryos cultured up to day 5-7, 516 became blastocysts: 123 were transferred on day 5 and 393 were cryopreserved. Comparisons of age, cleavage and blastocyst rate, quality of embryos, implantation success among PN score groups were evaluated by chi-square test or Kruskal-Wallis test as appropriate. Potential predictors of embryo implantation were first tested in univariable analysis using generalized estimating equations taking into account correlation between embryos originated from the same patient. Then, variables potentially associated with implantation success (P<0.05) were included in a multivariable analysis for calculating the adjusted odds ratio (OR) and 95% confidence interval (CI). RESULTS: There was no significant difference in patients'age, cleavage and blastulation rates, and embryo morphology among the three PNscore groups. The PN score 1-embryos had a greater implantation success respect to score 2-3-ones (OR 1.83; 95% CI 1.34-2.50, P=0.0001). Consistently, the pronuclear score remained predictive of implantation in top quality embryos (OR 1.68; 95%CI 1.17-2.42, P= 0.005). CONCLUSIONS: The consensus pronuclear score may be routinely included among criteria for embryo evaluation to increase patients' chance of becoming pregnant.

Trastuzumab Modulates the Protein Cargo of Extracellular Vesicles Released by ERBB2+ Breast Cancer Cells.

Cancers overexpressing the ERBB2 oncogene are aggressive and associated with a poor prognosis. Trastuzumab is an ERBB2 specific recombinant antibody employed for the treatment of these diseases since it blocks ERBB2 signaling causing growth arrest and survival inhibition. While the effects of Trastuzumab on ERBB2 cancer cells are well known, those on the extracellular vesicles (EVs) released from these cells are scarce. This study focused on ERBB2+ breast cancer cells and aimed to establish what type of EVs they release and whether Trastuzumab affects their morphology and molecular composition. To these aims, we performed immunoelectron microscopy, immunoblot, and high-resolution mass spectrometry analyses on EVs purified by differential centrifugation of culture supernatant. Here, we show that EVs released from ERBB2+ breast cancer cells are polymorphic in size and appearance and that ERBB2 is preferentially associated with large (120 nm) EVs. Moreover, we report that Trastuzumab (Tz) induces the expression of a specific glycosylated 50 kDa isoform of the CD63 tetraspanin and modulates the expression of 51 EVs proteins, including TOP1. Because these proteins are functionally associated with organelle organization, cytokinesis, and response to lipids, we suggest that Tz may influence these cellular processes in target cells at distant sites via modified EVs.

Occurrence of smooth endoplasmic reticulum aggregates in metaphase II oocytes: relationship with stimulation protocols and outcome of ICSI and IVF cycles.

STUDY QUESTION: Is there any association between the appearance of smooth endoplasmic reticulum aggregates (SERa) in oocytes and ovarian stimulation, embryological, clinical and neonatal outcomes of ICSI and IVF cycles? SUMMARY ANSWER: A suboptimal prolonged ovarian stimulation is detrimental to oocytes by inducing the occurrence of SERa, which reduces the reproductive potential of oocytes. WHAT IS KNOWN ALREADY: Controlled ovarian stimulation recruits oocytes of different qualities. Based on current evidence, it was agreed that non-homogeneous cytoplasm may represent the normal variability among oocytes rather than a dysmorphism with developmental significance. The only exception is the appearance of SERa within the ooplasm. Owing to the lack of univocal evidence in this literature about the safety of injecting oocytes with SERa and the mechanism responsible for the occurrence of SERa, this topic is still a matter of debate. STUDY DESIGN, SIZE, DURATION: A retrospective, longitudinal cohort study performed at a tertiary level public infertility center. We included 1662 cycles (180 SERa+ and 1482 SERa-) from 1129 women (age: 20-44 years) who underwent IVF/ICSI treatments in 2012-2019. The SERa+ cycles had at least one SERa+ oocyte in the oocyte cohort. The SERa- cycles had morphologically unaffected oocytes. PARTICIPANTS/MATERIALS, SETTING, METHODS: We collected stimulation data and embryological, clinical, neonatal outcomes of SERa- and SERa+ cycles and oocytes. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 347 out of 12 436 metaphase II oocytes (2.8%) were affected by SER. We performed only 12 transfers involving at least one SERa+ embryo. Stimulation length (P = 0.002), serum progesterone (P = 0.004) and follicle size (P = 0.046) at trigger, number of retrieved (P = 0.004) and metaphase II (P = 0.0001) oocytes were significantly higher in SERa+ than SERa- cycles. Fertilization rate was significantly (P < 0.0001) reduced in SERa+ cycles and oocytes compared to SERa- counterparts. Embryos of SERa+ cycles had a lower blastocyst formation rate compared to embryos of SERa- cycles (P = 0.059). Statistical analysis according to a generalized estimating equation model performed at patient level demonstrated that the duration of ovarian stimulation was predictive of SERa+ oocytes appearance. The clinical success of SERa+ cycles was lower than SERa- cycles, although no differences in neonatal birthweights or malformations were recorded in sibling unaffected oocytes of SERa+ cycles. LIMITATIONS, REASONS FOR CAUTION: Given that SERa+ oocytes were discarded in our center for years and transfers of embryos originating from affected oocytes were generally avoided, clinical outcomes of SERa+ cycles are largely attributable to the transfer of embryos derived from unaffected oocytes of SERa+ cycles and we did not have data about newborns from affected oocytes, since none of the transfers involving SERa+ embryos resulted in a progressive clinical pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: For the first time, we speculate that the late-follicular phase elevated serum progesterone caused by a suboptimal prolonged ovarian stimulation may be detrimental to the oocytes by inducing the occurrence of SERa, resulting in negative effects on their reproductive potential. This raises the question of whether some stimulation regimens could be worse than others and a change in stimulation protocol would reduce the possibility of producing oocytes with suboptimal maturation. In particular, our data highlight the importance of correct timing of the trigger in order to maximize oocyte collection, not only in terms of numerosity but also their reproductive potential. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Fifteen Year Regional Center Experience in Sperm Banking for Cancer Patients: Use and Reproductive Outcomes in Survivors.

Cancer treatments frequently impair the reproductive ability of patients by damaging spermatogenesis. International guidelines recommend semen cryopreservation to preserve the fertility of oncological adult males and pubertal boys. However, due to the low usage rate of banked samples, not a lot of data on assisted reproductive treatments (ART) success rates in this population and follow-up data for children born are available in the literature. The aims of this study were to report our 15 years of experience, the clinical outcomes of ART as well as neonatal characteristics of babies born. We retrospectively reviewed 682 oncological patients who were referred to our center from 2004 to 2019 for fertility preservation. Over the years, only 26 patients (4%) returned to use their sperm by ART. They were survivors of leukemia and lymphomas (52%), testicular cancer (20%), and other malignant diseases (28%). These couples performed 45 cycles: 34 intracytoplasmic sperm injection (ICSI) plus 11 frozen embryo transfers. A total of 13 children were born, with 35% of the cumulative live-birth delivery rate per couple. No stillbirths or malformations were recorded. These successful findings demonstrated that pregnancy could be safely achieved using frozen-thawed sperm of cancer survivors who cryopreserved before gonadotoxic therapies.

SARS-CoV-2 in the semen: Where does it come from?

BACKGROUND: The recent report of SARS-CoV-2 presence in semen samples of six patients, including two subjects who were recovering from the clinical disease, re-opened the discussion on possible male genital tract infection, virus shedding in semen, sexual transmission and safety of fertility treatments during the pandemic period. OBJECTIVES: To explore current data and hypothesis on the possible sites of SARS-CoV-2 infection in the male reproduction system. MATERIALS AND METHODS: We reviewed the current literature to describe: a) the evidences on angiotensin-converting enzyme 2 (AC2E) and transmembrane serine protease 2 (TMPRSS2) expression in the testes, accessory glands (including prostate) and the urinary tract; b) other coronaviruses' (SARS and MERS) ability to infect these sites. RESULTS: The co-expression of both ACE2 and TMPRSS2 genes was reported in spermatogonial stem cells, elongated spermatids, in at least a small percentage of prostate hillock cells and in renal tubular cells. Testicular damage was described in autopsies of SARS patients, without evidence of the virus in the specimens. Prostate is a known infection site for MERS-CoV. SARS-CoV-2 was detected in urines. DISCUSSION: There are still al lot of open questions on the effects of SARS-CoV-2 infection on the male reproductive tract. The presence of receptors is not a proof that the testis provides a site for viral infection and it is still unknown if SARS-CoV-2 is capable to pass the blood-testis barrier. The possibility of a prostate involvement has not been investigated yet: we have no data, but theoretically it cannot be excluded. Moreover, the RNA detected in semen could have been just a residual of urinary shedding. CONCLUSION: Opening our prospective beyond the testis could be the key to better understand the possibility of a semen-related viral transmission as well as COVID19 short and long-term effects on male reproductive function.

Prexasertib: an investigational checkpoint kinase inhibitor for the treatment of high-grade serous ovarian cancer.

Introduction Patients with high-grade serous ovarian cancer (HGSOC) have a poor prognosis, and current chemotherapy regimens for treating advanced disease are far from satisfactory. Prexasertib (LY2606368) is a novel checkpoint kinase inhibitor (CHK) under investigation for the treatment of HGSOC. Data from a recent phase II trial showed promising efficacy and safety results for treating wild-type BRCA HGSOC. Areas covered This article reviews the available data on the pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of prexasertib in the treatment of HGSOC. Expert opinion Until now, prexasertib demonstrated clinical activity in phase I and II clinical trial for treating wild-type BRCA HGSOC, whereas its promising efficacy as monotherapy and combined with olaparib in BRCA-mutated HGSOC has been preliminary evidenced only in phase I studies. Compared to other drugs of the same class, prexasertib showed a better tolerability profile, causing moderate hematological toxicity. Further studies are needed to confirm efficacy and safety profiles of prexasertib in combined regimens. New early clinical trials may investigate prexasertib administered with programmed cell death ligand 1 (PD-L1) and PI3 K inhibitors due to the preclinical evidence of a synergic action.

Borderline ovarian tumours: management in the era of fertility-sparing surgery.

Borderline ovarian tumours (BOTs) are ovarian neoplasms characterised by epithelial proliferation, variable nuclear atypia and no evidence of destructive stromal invasion. BOTs account for approximately 15% of all epithelial ovarian cancers. Due to the fact that the majority of BOTs occur in women under 40 years of age, their surgical management often has to consider fertility-sparing approaches. The aim of this mini-review is to discuss the state of the art of fertility-sparing surgery for BOTs with a specific focus on the extent of surgery, post-operative management and fertility.