Understanding seminal plasma in male infertility: emerging markers and their implications.

Infertility affects a significant proportion of the reproductive-aged population, with male-associated factors contributing to over half of the cases. However, current diagnostic tools have limitations, leading to an underestimation of the true prevalence of male infertility. While traditional semen parameters provide some insights, they fail to determine the true fertility potential in a substantial number of instances. Therefore, it is crucial to investigate additional molecular targets responsible for male infertility to improve understanding and identification of such cases. Seminal plasma, the main carrier of molecules derived from male reproductive glands, plays a crucial role in reproduction. Amongst its multifarious functions, it regulates processes such as sperm capacitation, sperm protection and maturation, and even interaction with the egg's zona pellucida. Seminal plasma offers a non-invasive sample for urogenital diagnostics and has shown promise in identifying biomarkers associated with male reproductive disorders. This review aims to provide an updated and comprehensive overview of seminal plasma in the diagnosis of male infertility, exploring its composition, function, methods used for analysis, and the application of emerging markers. Apart from the application, the potential challenges of seminal plasma analysis such as standardisation, marker interpretation and confounding factors have also been addressed. Moreover, we have also explored future avenues for enhancing its utility and its role in improving diagnostic strategies. Through comprehensive exploration of seminal plasma's diagnostic potential, the present analysis seeks to advance the understanding of male infertility and its effective management.

Male Contributory Factors in Recurrent Pregnancy Loss.

With 40% of idiopathic cases, recurrent pregnancy loss (RPL) is a problem of great concern for patients and clinicians. In addition to financial burden, it causes a lot of frustration and anxiety in affected couples. The primary objective of this review was to gain knowledge of recent advances in the field of recurrent pregnancy losses and to understand the role of male contributory factors in idiopathic cases. For a long time, researchers and clinicians were seeking an explanation for idiopathic RPL (iRPL) in females only; however, with recent advances in reproductive biology, the role of spermatozoa in early embryonic development has caught the attention of researchers. Clinically, only routine semen parameters and karyotyping are investigated in iRPL male partners, which seem to be insufficient in the present scenario, and thus, more information at the molecular level is required for a comprehensive understanding of iRPL. In concluding remarks, we suggest targeted multi-omics investigations in a large cohort to improve our understanding of the role of male contributory factors in iRPL.

The effect of paternal and maternal factors on the prognosis of live birth in couples with recurrent pregnancy loss.

INTRODUCTION: Currently, recurrent pregnancy loss (RPL) examinations focus on the woman, although paternal factors are also involved. Men in couples with RPL have higher sperm DNA fragmentation levels than fertile men, but the effect of sperm DNA damage on couple's later prognosis is unknown. Advanced maternal age and obesity are associated with RPL, but paternal lifestyle factors are less studied. Therefore, we aimed to study the associations of couples' lifestyle factors, causes of RPL, and sperm DNA fragmentation with their prognosis of future live birth. MATERIAL AND METHODS: This descriptive cohort study comprised 506 couples investigated for RPL at Helsinki University Hospital, Finland, between 2007 and 2016, linked with national health and population registers. The primary outcome was couple's live birth after RPL investigations. Data on couple's background factors, including age, body mass index, smoking, and alcohol use, were collected from medical records. Sperm DNA fragmentation index was analyzed from 211 men using the sperm chromatin dispersion test. The associations between background factors, sperm DNA fragmentation, and cumulative probability of live birth over time were analyzed using cross-tabulations and age-adjusted Cox regression. RESULTS: In all, 352 of 506 couples (69.6%) achieved live birth. Maternal age, unexplained RPL, prolonged pregnancy attempts before investigations, paternal obesity, and maternal smoking were associated with prognosis: unadjusted hazard ratio for couple's live birth for women aged 35-39 vs younger than 30 years was 0.63 (95% confidence interval [CI] 0.47-0.84), and for 40 years or older was 0.36 (95% CI 0.22-0.58). Age-adjusted hazard ratio for unexplained vs explained RPL was 1.39 (95% CI 1.12-1.72), for couple's pregnancy attempt at least 4 years vs less than 2 years was 0.50 (95% CI 0.33-0.76), for paternal body mass index at least 30 kg/m2 vs less than 25 kg/m2 was 0.67 (95% CI 0.46-0.98), and for maternal smoking was 0.71 (95% CI 0.51-0.99). Altogether, 96/135 (71.1%) couples with normal (<15%), 38/60 (63.3%) with intermediate (15-30%), and 11/16 (68.8%) with high sperm DNA fragmentation index achieved live birth (p = 0.56). CONCLUSIONS: In couples with RPL, prolonged pregnancy attempts, a cause found in RPL examinations, lifestyle factors, and maternal age are negatively associated with their prognosis of future live birth. Sperm DNA fragmentation was not associated, but the number of men with damaged spermatozoa was small. We suggest that clinicians include women and men in RPL counseling because couple's joint lifestyle seems to determine their later prognosis.

Toward more accurate prediction of future pregnancy outcome in couples with unexplained recurrent pregnancy loss: taking both partners into account.

OBJECTIVE: To identify, besides maternal age and the number of previous pregnancy losses, additional characteristics of couples with unexplained recurrent pregnancy loss (RPL) that improve the prediction of an ongoing pregnancy. DESIGN: Hospital-based cohort study in couples who visited specialized RPL units of two academic centers between 2012 and 2020. SETTING: Two academic centers in the Netherlands. PATIENTS: Clinical data from 526 couples with unexplained RPL were used in this study. INTERVENTION(S): None. MAIN OUTCOME MEASURES: The final model to estimate the chance of a subsequent ongoing pregnancy was determined using a backward selection process and internally validated using bootstrapping. Model performance was assessed in terms of calibration and discrimination (area under the receiver operating characteristic curve). RESULTS: Subsequent ongoing pregnancy was achieved in 345 of 526 couples (66%). The number of previous pregnancy losses, maternal age, paternal age, maternal body mass index, paternal body mass index, maternal smoking status, and previous in vitro fertilization/intracytoplasmic sperm injection treatment were predictive of the outcome. The optimism-corrected area under the receiver operating characteristic curve was 0.63 compared with 0.57 when using only the number of previous pregnancy losses and maternal age. CONCLUSIONS: The identification of additional predictors of a subsequent ongoing pregnancy after RPL, including male characteristics, is significant for both clinicians and couples with RPL. At the same time, we showed that the predictive ability of the current model is still limited and more research is warranted to develop a model that can be used in clinical practice.

Association Between Male Use of Pain Medication and Fecundability.

Administration of pain relievers has been associated with both lower and higher risks of adverse reproductive outcomes in animals. In the sole investigation of male pain-reliever use and human fertility carried out to date, Smarr et al. (Hum Reprod. 2016;31(9):2119-2127) found a 35% reduction in fecundability among males with urinary acetaminophen concentrations in the highest quartile (>73.5 ng/mL) versus the lowest (<5.4 ng/mL). We analyzed data from 1,956 males participating in Pregnancy Study Online, a preconception cohort study of North American couples enrolled between 2013 and 2019. Males and females completed baseline questionnaires on sociodemographic characteristics, lifestyle, medication use, and medical history; females completed bimonthly follow-up questionnaires for up to 12 months. We categorized pain medications by active ingredient (ibuprofen, acetaminophen, naproxen, aspirin) and cumulative monthly dose. We used proportional probabilities models to calculate fecundability ratios and 95% confidence intervals, adjusting for potential confounders. In the 4 weeks before baseline, 51.7% of males used pain medications. Adjusted fecundability ratios were 1.02 for ibuprofen (95% confidence interval (CI): 0.91, 1.13), 0.89 for acetaminophen (95% CI: 0.77, 1.03), 1.07 for naproxen (95% CI: 0.85, 1.35), and 1.05 for aspirin (95% CI: 0.81, 1.35), as compared with nonuse of each medication. In this study, male use of pain medications at low doses was not notably associated with fecundability.

The Outcome of Assisted Reproductive Techniques among Couples with Male Factors at Prince Khalid Bin Sultan Fertility Centre, Kingdom of Saudi Arabia.

BACKGROUND: Thirty-three percent of infertility due to paternal factors, there are an increasing proportion of couples who decide to conceive by assisted reproductive techniques (ART). The outcome prediction is pivotal for decision making. AIM: We aimed to study the pregnancy outcomes of different ART with male factors infertility. METHODS: This is retrospective cross-sectional study conducted at Tabuk, Kingdom of Saudi Arabia. One hundred fifteen patients' records reviewed using a structured checklist to collect demographic data, sperm (concentration, motility, and morphology). Female with significant infertility factor were excluded. Chi-square was used for the outcome of various ART. RESULTS: Out of 115 couples with male factors; treated by Intracytoplasmic Sperm Injection (ICSI), In Vitro Fertilization (IVF) and Intrauterine Insemination (IUI); the mean age was 35.2 ± 6.3 years for men and 29.7 ± 5.1 for females. IVF had the highest success rate overall and had a high pregnancy rate with oligospermia and asthenospermia. ICSI has a good outcome for those with azoospermia, severe oligospermia, and teratozoospermia. IUI must be tried as a first line treatment when semen concentration is more than 10 million sperm/ml. all are not significant (P > 0.05). CONCLUSION: No significant differences were reported in the pregnancy outcome between various assisted reproductive techniques, smoking, type of infertility and medication.

Infertilidad masculina / Male infertility

Se estima que aproximadamente un 15 por ciento de las parejas son incapaces de concebir luego de un año de relaciones sexuales no protegidas; 30 por ciento son debidas a factor femenino y 30 por ciento a factor masculino. El 40 por ciento restante es de causa mixta. La evaluación inicial de rutina en el varón (que incluye una detallada historia clínica, examen físico y test básicos como perfil hormonal y análisis seminal) es por lo tanto esencial para la mejoría de su fertilidad. El varicocele, criptorquidia no tratada y las infecciones del tracto urogenital son las causas identificables más frecuentes de infertilidad masculina. Causas menos frecuentes son las disfunciones sexuales, trastornos endocrinos y efectos adversos de medicamentos. Los tratamientos para estas patologías han sido efectivos en la mayoría de los casos, permitiendo a un importante número de parejas concebir en forma espontánea. Si esto no es posible, las parejas pueden recurrir a técnicas de reproducción asistida de baja complejidad, tales como la Inseminación Intrauterina. Y sólo en aquellos casos con problemas más severos recurriremos a técnicas de reproducción de alta complejidad como por ejemplo el ICSI (Inyección Intracitoplasmática de Espermatozoides). Importantes progresos en el área de la Microcirugía permiten no sólo reparar la vía seminal en muchos casos, sino también recuperar espermatozoides de pacientes con atrofia testicular. En los últimos años, junto con el ICSI, han sido una importante contribución.

It is estimated that approximately 15 percent of couples are unable to conceive after one year of contraceptive-free intercourse; 30 percent of which are due to female factors and 30 percent to malefactors. The remaining 40 percent are due to both partners. A routine initial evaluation of the male partner (including detailed medical history, physical exam and basic tests such as hormonal profile and semen analysis) is therefore essential, for improvement of their fertility. Varicocele, untreated Cryptorquidism, infections (eg. epididymitis, orquitis, prostatitis and vesiculitis, most of which are related with sexually transmitted diseases) are the most frequent causes of male infertility. Other minor causes include sexual dysfunctions, drug adverse effects, exposure to radiationor contaminants, endocrine and genetic factors. Treatment for this condition has been effective in most cases, allowing a significant proportion of couples to conceive spontaneously. Whenever this is not possible, patients may resort to low complexity techniques such as artificial insemination, and only in more severe cases, to advanced assisted reproduction techniques such as In Vitro Fertilization (IVF) and in particular Intracytoplasmic Sperm injection (ICSI).Microsurgery has also progressed. Not only used to repair the seminal path when obstructed, but also to recover sperm from patients with testicular atrophy. In recent years, these techniques, together with ICSI, have made an important therapeutic contribution.