Search

Background: Infertility impacts 16% of North American couples, with male factor infertility contributing to ∼30% of cases. Reproductive hormones, especially testosterone, are essential for spermatogenesis. An age-independent population-level decline in testosterone concentrations over the past few decades has been proposed to be a consequence of diet and lifestyle changes. Vitamin B 12 is present in the testes and has been suggested as an adjuvant nutritional therapy for male infertility due to its potential to improve sperm parameters. However, evidence examining the relationship between vitamin B 12 and reproductive hormones is limited., Objectives: The objective was to cross-sectionally examine the relationship between serum vitamin B 12 and male reproductive hormones (luteinizing hormone, follicular stimulating hormone, total testosterone, estradiol, and prolactin)., Methods: Men with infertility (n = 303) were recruited from Mount Sinai Hospital in Toronto, Canada. Serum was analyzed for vitamin B 12 and reproductive hormones. Statistical analyses included nonparametric Spearman's rank correlation coefficient, linear regression, logistic regression, and effect modification by age and BMI linear regressions., Results: An independent monotonic relationship between serum vitamin B 12 and total testosterone (ρ = 0.19, P = 0.001) was observed. Serum vitamin B 12 was linearly associated with total testosterone (unadjusted β = 0.0007, P = 0.008 and adjusted β = 0.0005, P = 0.03). Compared to individuals in the lowest tertile of serum vitamin B 12 , those in the middle tertile (adjusted odds ratio [OR] = 0.48; 95% confidence interval [CI]: 0.25, 0.93, P = 0.03) and the highest tertile (unadjusted OR = 0.41; 95% CI: 0.22, 0.77, P = 0.005 and adjusted OR = 0.44; 95% CI: 0.22, 0.87, P = 0.02) had reduced odds of testosterone deficiency., Conclusions: These findings suggest that among men with infertility, low serum vitamin B 12 is associated with a higher risk of testosterone deficiency and impaired androgenic hormonal profiles that impact spermatogenesis and consequently, fertility., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Grafting of cryopreserved testicular tissue is a promising tool for fertility and testicular function preservation in endangered species, mutant animals, or cancer patients for future use. In this study, we aimed to improve the whole neonatal mouse testicular tissue cryopreservation protocols by comparing cryosurvival, spermatogenesis, and androgen production of grafted testicular tissue after cryopreservation with three different vitrification protocols and an automated computed controlled-rate freezing. Whole neonatal mouse testes were vitrified with various vitrification solutions (V1) 40% EG + 18% Ficoll + 0.35 M Sucrose, (V2) DAP 213 (2 M DMSO + 1 M Acetamid + 3 M PG), or (V3) 15% EG + 15% PG + 0.5 M Sucrose (total solute concentration V1:74.34%, V2:44.0%, and V3:49.22% wt/vol). Alternatively, neonatal testicular tissue was also frozen in 0.7 M DMSO +5% fetal bovine serum using controlled-rate freezing and compared to fresh grafted testicular tissue, sham grafted controls, and the vitrification protocol groups. Fresh (n = 4) and frozen-thawed (n = 4) testes tissues were grafted onto the flank of castrated male NCr Nude recipient mouse. The grafts were harvested after three months. Fresh or frozen-thawed grafts with controlled-rate freezing had the highest rate of tissue survival compared to other vitrified protocols after harvesting (p < 0.05). Both controlled-rate freezing and V1 protocol groups displayed the most advanced stages of spermatogenesis with elongated spermatids and spermatozoa in 17.6 ± 1.3% and 16.3 ± 1.9% of seminiferous tubules based on histopathological evaluation, respectively. Hosts of the testicular graft from controlled-rate freezing had higher levels of serum testosterone compared to all other vitrified-thawed graft groups (p < 0.05). This study shows that completed spermatogenesis from whole neonatal mouse testes were obtained when frozen with controlled-rate freezing and V1 vitrification solution and that testicular cryopreservation efficacy vary with the protocol and vitrification technique., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Restoration of male fertility associated with use of the cryopreserved testicular tissue would be a significant advance in human and animal assisted reproductive technology. The purpose of this study was to test the effects of four different cryoprotectant agents (CPA) on spermatogenesis and steroidogenesis in cryopreserved and allotransplanted neonatal mouse testicular tissue. Hank's balanced salt solution (HBSS) with 5% fetal bovine serum including either 0.7 M dimethyl sulfoxide (DMSO), 0.7 M propylene glycol (PrOH), 0.7 M ethylene glycol (EG), or glycerol was used as the cryoprotectant solution. Donor testes were collected and dissected from neonatal pups of CD-1 mice (one day old). Freezing and seeding of the testicular whole tissues was performed using an automated controlled-rate freezer. Four fresh (non-frozen) or frozen-thawed pieces of testes were subcutaneously grafted onto the hind flank of each castrated male NCr nude recipient mouse and harvested after 3 months. Fresh neonatal testes grafts recovered from transplant sites had the most advanced rate of spermatogenesis with elongated spermatid and spermatozoa in 46.6% of seminiferous tubules and had higher levels of serum testosterone compared to all other frozen-thawed-graft groups (p<0.05). Fresh grafts and frozen-thawed grafts in the DMSO group had the highest rate of tissue survival compared to PrOH, EG, and glycerol after harvesting (p>0.05). The most effective CPA for the freezing and thawing of neonatal mouse testes was DMSO in comparison with EG (p<0.05) in both pre-grafted and post-grafted tissues based on histopathological evaluation. Likewise, the highest level of serum testosterone was obtained from the DMSO CPA group compared to all other cryoprotectants evaluated (p<0.05). The typical damage observed in the frozen-thawed grafts included disruption of the interstitial stroma, intercellular connection ruptures, and detachment of spermatogonia from the basement membrane. These findings indicate that neonatal mouse testes were most effectively preserved when frozen with HBSS medium with DMSO and that the type of CPA is a significant factor to obtain the most advanced stages of spermatogenesis and steroidogenesis after cryopreservation, thawing, and transplantation of neonatal mouse testes., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Several diseases have been clinically or genetically related to cystic fibrosis (CF), but a consensus definition is lacking. Here, we present a proposal for consensus guidelines on cystic fibrosis transmembrane conductance regulator (CFTR)-related disorders (CFTR-RDs), reached after expert discussion and two dedicated workshops. A CFTR-RD may be defined as "a clinical entity associated with CFTR dysfunction that does not fulfil diagnostic criteria for CF". The utility of sweat testing, mutation analysis, nasal potential difference, and/or intestinal current measurement for the differential diagnosis of CF and CFTR-RD is discussed. Algorithms which use genetic and functional diagnostic tests to distinguish CF and CFTR-RDs are presented. According to present knowledge, congenital bilateral absence of vas deferens (CBAVD), acute recurrent or chronic pancreatitis and disseminated bronchiectasis, all with CFTR dysfunction, are CFTR-RDs., (Copyright © 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Objective: It has been well-documented that the use of assisted reproductive technology (ART) increases the risk for multiple births, which are associated with sub-optimal outcomes for pregnant women and their offspring. The occurrence of multiple births due to infertility treatments has been recognized as a significant problem globally, and a number of countries have developed approaches, policies, statutes, and regulations geared to decreasing the rates of multiple births as a result of ART. This review was designed to explore Canada's position in the international context of ART-related multiple births and to examine the strategies of other countries intended to decrease rates of multiple pregnancy., Methods: Data were obtained from publicly available data sources from 21 countries, including Canada, and comparisons were made between pregnancy rates, percentages of live births, percentages of multiple births, numbers of embryos transferred, and governing guidelines and policies., Results: Canada has one of the highest ART-related multiple-birth rates, and the number of embryos transferred per cycle plays an important role in this. Cooperation among stakeholders in the development of approaches and guidelines is essential for preventing multiple births due to infertility treatments., Conclusions: In order effectively to reduce the multiple-birth rate in Canada, it is important to learn from the experiences of other countries, taking the Canadian context into consideration.

The first objective was to compare sperm quality following conventional manual sperm freezing (cryovials held 1, 2, 3, and 4 cm, respectively, above liquid nitrogen (LN(2)) for 10 min, resulting in cooling velocities of approximately -14.9, -10.1, -6.6, and -5.1 °C/min, respectively), and cooling velocities of -5, -20, -40, and -100 °C/min in a programmed automated freezer, for sperm recovered from CD-1, B6129SF1, and C57BL/6NCrlBR mice. Furthermore, using these strains, as well as 129S/SvPaslco, and DBA/2NCrlBR mice, the second objective was to determine the effects on DNA integrity of sperm exposed to hyposmotic (1 mOsm/L) and hyperosmotic (2400 mOsm/L) solutions, compared to an isosmotic control (300 mOsm/L). For freezing above LN(2) or in an automated freezer, 2 cm above LN(2) and -100 °C/min, respectively, were optimal (P < 0.05-0.01), with no significant differences between these two approaches for post-thaw progressive motility, DNA integrity, and in vitro rates of fertilization and blastocyst formation. Both manual and automated freezing techniques increased post-thaw sperm DNA fragmentation (P < 0.01); the DNA integrity of post-thaw sperm was significantly affected by cooling velocity and strain background. Relative to isosmotic controls, a hyposmotic solution was more deleterious (P < 0.05-0.01) to sperm DNA integrity than a hyperosmotic solution for CD-1, B6129SF1, C57BL/6, and DBA mice (there were strain-dependent differences). In conclusion, optimization of freezing distance and cooling velocity (manual and automated freezing, respectively) were significant factors for efficient cryopreservation and re-derivation of mice from frozen-thawed sperm. Additionally, osmotically-driven volume changes in mouse sperm increased DNA fragmentation, with susceptibility affected by background strain., (Crown Copyright © 2010. Published by Elsevier Inc. All rights reserved.)

Men with high sperm DNA damage have a reduced fertility potential. Correlation of specific clinical factors to the degree of sperm DNA damage remains unclear. This retrospective study evaluated the frequency and severity of sperm DNA damage in men with different aetiologies of male factor infertility. Patients with male factor infertility (n=288) underwent flow cytometry-based sperm DNA damage assessment and results were correlated with the major aetiologies of male infertility: varicocele, bacteriospermia and idiopathic infertility. Sperm DNA damage was significantly correlated to the patient's age, sperm motility, normal morphology and vitality (P < 0.001). High sperm DNA damage (30%) was most frequently found in the group with bacteriospermia (48%), compared with 30% of the men with varicoceles and 22% of the men with idiopathic infertility (P < 0.02). While some tendency was observed for a correlation of increasing sperm DNA damage in patients with grade III and bilateral varicoceles, this difference did not reach statistical significance. The data support the importance of proper physical and laboratory investigations of the fertility status in men to correctly diagnose and treat male infertility., (2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

We report the peripartum management of a 29-year-old primigravid patient with neurocardiogenic syncope, which had been diagnosed six years previously on tilt-table testing. General principles were applied to minimise the risk of precipitating syncopal episodes. She had an uneventful ventouse-assisted vaginal delivery under epidural anaesthesia in our obstetric high dependency unit. The optimum management of these patients has yet to be established.

Background: There are currently limited treatment options available to modify the appearance of scarring due to deliberate self-harm (DSH). The authors present two cases of Integra dermal matrix use for resurfacing scars due to past DSH., Methods: By excising the scars and resurfacing with Integra, we present and describe a novel technique for treating the visible stigmata of previous DSH., Results: No complications occurred, and patients noted improved appearance, skin quality and self-esteem following surgery. Both patients would recommend this treatment to others., Conclusions: Integra dermal matrix substitute may be used successfully to treat scarring from previous DSH.

Spermatozoan maturation, motility, and fertility are, in part, dependent upon the progressive increase in epididymal and spermatozoal carnitine, critical for mitochondrial fatty acid oxidation, as sperm pass from the caput to the cauda of the epididymis. We demonstrate that the organic cation/carnitine transporters, OCTN1, OCTN2, and OCTN3, are expressed in sperm as three distinct proteins with an expected molecular mass of 63 kDa, using Western blot analysis and our transporter-specific antibodies. Carnitine uptake studies in normal control human sperm samples further support the presence of high-affinity (OCTN2) carnitine uptake (K(m) of 3.39+/-1.16 microM; V(max) of 0.23+/-0.14 pmol/min/mg sperm protein; and mean+/-SD; n=12), intermediate-affinity (OCTN3) carnitine uptake (K(m) of 25.9+/-14.7 microM; V(max) of 1.49+/-1.03 pmol/min/mg protein; n=26), and low-affinity (OCTN1) carnitine uptake (K(m) of 412.6+/-191 microM; V(max) of 32.7+/-20.5 pmol/min/mg protein; n=18). Identification of individuals with defective sperm carnitine transport may provide potentially treatable etiologies of male infertility, responsive to L-carnitine supplementation.