Lack of trusted diagnostic tools for undetermined male infertility

Pandruvada, Swati; Royfman, Rachel; Shah, T.; Sindhwani, Puneet; Dupree, James M.; Schon, Samantha B.; Avidor‐Reiss, Tomer

doi:10.1007/s10815-020-02037-5

Cited by 28 publications

(24 citation statements)

References 123 publications

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“…Yet, these parameters are not universal for predicting fertilisation success. It was shown that about 50% of couples undergoing an IVF (in vitro fertilisation) programme with failed fertilisation had normal pre-IVF semen analysis [ 1 , 2 ]. A similar case has been reported for the artificial insemination (AI) bulls, for which the computer-assisted sperm analysis (CASA) results exceeded the minimal accepted values and showed over 92% motile sperm of normal morphology and DNA integrity.…”

Section: Introductionmentioning

confidence: 99%

Mitochondria Content and Activity Are Crucial Parameters for Bull Sperm Quality Evaluation

et al. 2021

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Standard sperm evaluation parameters do not enable predicting their ability to survive cryopreservation. Mitochondria are highly prone to suffer injuries during freezing, and any abnormalities in their morphology or function are reflected by a decline of sperm quality. Our work focused on describing a link between the number and the activity of mitochondria, with an aim to validate its applicability as a biomarker of bovine sperm quality. Cryopreserved sperm collected from bulls with high (group 1) and low (group 2) semen quality was separated by swim up. The spermatozoa of group 1 overall retained more mitochondria (MitoTrackerGreen) and mtDNA copies, irrespective of the fraction. Regardless of the initial ejaculate quality, the motile sperm contained significantly more mitochondria and mtDNA copies. The same trend was observed for mitochondrial membrane potential (ΔΨm, JC-1), where motile sperm displayed high ΔΨm. These results stay in agreement with transcript-level evaluation (real-time polymerase chain reaction, PCR) of antioxidant enzymes (PRDX1, SOD1, GSS), which protect cells from the reactive oxygen species. An overall higher level of glutathione synthetase (GSS) mRNA was noted in group 1 bulls, suggesting higher ability to counteract free radicals. No differences were noted between basal oxygen consumption rate (OCR) (Seahorse XF Agilent) and ATP-linked respiration for group 1 and 2 bulls. In conclusion, mitochondrial content and activity may be used as reliable markers for bovine sperm quality evaluation.

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Section: Introductionmentioning

confidence: 99%

Mitochondria Content and Activity Are Crucial Parameters for Bull Sperm Quality Evaluation

et al. 2021

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“…One reason infertility treatments fail is deficiencies in identifying the underlying causes of male factor reproductive diseases. About 25% of male factor infertility (Pandruvada et al, 2021), 33% of infertility in couples (Smith et al, 2003), 50% of recurrent miscarriages (Garrido-Gimenez and Alijotas-Reig, 2015), and most embryo development defects are unexplained (Reefhuis et al, 2015). Furthermore, intracytoplasmic sperm injection (ICSI) is only successful at leading to clinical pregnancy in 1 out of 2 treated women, and often this requires multiple cycles of treatment (Stern et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Fluorescence-Based Ratiometric Analysis of Sperm Centrioles (FRAC) Finds Patient Age and Sperm Morphology Are Associated With Centriole Quality

Turner

Fishman

Asadullah

et al. 2021

Front. Cell Dev. Biol.

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A large proportion of infertility and miscarriage causes are unknown. One potential cause is a defective sperm centriole, a subcellular structure essential for sperm motility and embryonic development. Yet, the extent to which centriolar maladies contribute to male infertility is unknown due to the lack of a convenient way to assess centriole quality. We developed a robust, location-based, ratiometric assay to overcome this roadblock, the Fluorescence-based Ratiometric Assessment of Centrioles (FRAC). We performed a case series study with semen samples from 33 patients, separated using differential gradient centrifugation into higher-grade (pellet) and lower-grade (interface) sperm fractions. Using a reference population of higher-grade sperm from infertile men with morphologically standard sperm, we found that 79% of higher-grade sperm of infertile men with substandard sperm morphology have suboptimal centrioles (P = 0.0005). Moreover, tubulin labeling of the sperm distal centriole correlates negatively with age (P = 0.004, R = −0.66). These findings suggest that FRAC is a sensitive method and that patient age and sperm morphology are associated with centriole quality.

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“…It will be interesting to test whether the reference values described can distinguish between these conditions. Men who attend fertility clinics seek fertility advice, but not all men with abnormal sperm parameters are infertile and vice versa (Guzick et al, 2001;Cairo Consensus Workshop Group, 2020;Pandruvada et al, 2021). Infertility with normal semen parameters is one of the new challenges in this field.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial metabolism determines the functional status of human sperm and correlates with semen parameters

Irigoyen

Pintos-Polasky

Rosa-Villagrán

et al. 2022

Front. Cell Dev. Biol.

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The diagnosis of male infertility is based essentially on the patient’s medical history and a standard semen analysis. However, the latter rarely provides information on the causes of a possible infertility, emphasizing the need to extend the analysis of the sperm function. Mitochondrial function has been associated with sperm function and dysfunction, the latter primarily through the production of excessive amounts of reactive oxygen species (ROS). We hypothesized that analysis of sperm mitochondrial metabolism together with sperm ROS production could be an additional tool to improve routine semen analysis, after appropriate validations. To test our hypothesis, we performed several experiments using a non-routine method (high-resolution respirometry, HRR) to access mitochondrial function. First, we investigated whether mitochondrial function is related to human sperm motility and morphology. When mitochondrial metabolism was challenged, sperm motility decreased significantly. Additionally, morphological abnormalities in the sperm mid-piece and mitochondria were associated with global sperm defects evaluated by routine methods. Subsequently, sperm mitochondrial function was assessed by HRR. Respiratory control ratio (RCR) was determined and evaluated in the context of classical sperm analysis. In parallel, sperm hydrogen peroxide (H2O2) production and seminal plasma (SP) antioxidant capacity were measured. The percentage of sperm with progressive motility correlated positively with RCR, SP antioxidant capacity, and negatively with the concentration of extracellular H2O2 production ([H2O2]). The percentage of normal sperm morphology correlated positively with RCR and negatively with [H2O2]. Sperm morphology did not correlate with seminal plasma antioxidant capacity. Furthermore, Receiver Operating Characteristic curves were used for the first time to test the diagnostic ability of RCR, [H2O2], and SP antioxidant capacity as binary classifiers. An RCR cut off value of 3.2 was established with a sensitivity of 73% and a specificity of 61%, using reference values considered normal or abnormal in routine semen analysis. The cut off value for [H2O2] was 0.2 μM/106 sperm (sensitivity = 65%, specificity = 60%). There were no reference values for SP antioxidant capacity that distinguished between abnormal and normal sperm samples. We conclude that sperm mitochondrial function indices in combination with [H2O2] may be useful tools to complement the routine semen analysis.

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Lack of trusted diagnostic tools for undetermined male infertility

Cited by 28 publications

References 123 publications

Mitochondria Content and Activity Are Crucial Parameters for Bull Sperm Quality Evaluation

Mitochondria Content and Activity Are Crucial Parameters for Bull Sperm Quality Evaluation

Fluorescence-Based Ratiometric Analysis of Sperm Centrioles (FRAC) Finds Patient Age and Sperm Morphology Are Associated With Centriole Quality

Mitochondrial metabolism determines the functional status of human sperm and correlates with semen parameters

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