Primer- Male infertility

[madman]

Abstract

Clinical infertility is the inability of a couple to conceive after 12 months of trying. Male factors are estimated to contribute to 30–50% of cases of infertility. Infertility or reduced fertility can result from testicular dysfunction, endocrinopathies, lifestyle factors (such as tobacco and obesity), congenital anatomical factors, gonadotoxic exposures, and aging, among others. The evaluation of male infertility includes detailed history taking, focused physical examination, and selective laboratory testing, including semen analysis. Treatments include lifestyle optimization, empirical or targeted medical therapy as well as surgical therapies that lead to measurable improvement in fertility. Although male infertility is recognized as a disease with effects on the quality of life for both members of the infertile couple, fewer data exist on specific quantification and impact compared with other health-related conditions.




Epidemiology

*Prevalence
*Health-related issues
*Genetic and congenital conditions



Mechanisms/pathophysiology

*The hypothalamic-pituitary-gonadal axis
*Sertoli cells
*Peritubular myoid cells
*Leydig cells
*The germ cells in the testis
*Mitosis in the seminiferous tubule
*Meiosis
*Spermiogenesis
*The cycle and stages of spermatogenesis
*Leydig cells and androgens in men
*Exposures leading to dysfunction
*Importance of paternal aging




Diagnosis, screening, and prevention

*Surgical history
*Systemic medical illness
*Lifestyle
*Medications
*Physical examination


*Laboratory assessment
-Semen analysis
-Endocrine evaluation
-Genetics studies
-Selective imaging




Management

*General treatments
-Lifestyle interventions
-Limiting environmental exposures


*Focused therapy
-Pharmacological treatments
-Surgical therapy


*Quality of life




Outlook

*Future diagnostics and treatments
*Required public health measures

 

[madman]

Box 1

 

[madman]

Fig. 1 | Global fertility rates. The fertility rate refers to the number of children per reproductive-age woman. A rate of 2.1 is considered necessary for a steady state of a population excluding immigration. Thus, fertility rates of <2.1 suggest that population numbers would be expected to decline over time if no immigration occurs. Reprinted from ref. 303, CC BY 4.0 (CC BY 4.0 Deed | Attribution 4.0 International | Creative Commons), based on data from the United Nations, World PopulationProspects (2022)304

 

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Box 2

 

[madman]

Fig. 2 | Anatomy of the male reproductive tract. Spermatogenesis occurs inthe testis. Sperm then moves through the rete testis to the epididymis wheresperm maturation is completed. Sperm then traverses the vas deferens againstgravity into the pelvis. Sperm is stored in the ampulla of the vas deferens untilejaculation. On ejaculation, fluid from the vasa deferentia and prostate areexpelled into the posterior urethra followed by fluid from the seminal vesicles.The ejaculate is then expelled from the urethra.

 

[madman]

Fig. 3 | The role of the hypothalamic–pituitary–gonadal axis in male fertility. The hypothalamus secretes gonadotropin-releasing hormone (GnRH), which stimulates the anterior pituitary gland to secrete the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH stimulates the Leydig cells in the testis to produce testosterone. FSH stimulates Sertoli cells to induce spermatogenesis. Negative feedback from the testes to the hypothalamus and pituitary occurs through the production of inhibin by Sertoli cells and testosterone (via peripheral conversion into oestradiol).

 

[madman]

Table 1 | The major organs, cell types, hormones, paracrine factors, and receptors that regulate human spermatogenesis

 

[madman]

Fig. 4 | Stages of spermatogenesis in mice and humans. a,b, Stages of spermatogenesis in mouse and human based on germ cell associations and morphology. Sections of mouse and human testes are stained with periodic acid–Schiff reagent (PAS)–hematoxylin. Spermatogenesis is the process of sperm development and involves phases of mitosis, meiosis, and spermiogenesis (morphological cell changes). Spermatogenesis is divided into12 stages (I–XII) and 16 spermatid developmental steps (1–16) in mice (part a)and six stages (I–VI) and six spermatid developmental steps (Sa, Sb1, Sb2, Sc, Sd1, and Sd2) in humans (part b). 2°, secondary spermatocytes; MA, meioticanaphase; A, type A spermatogonia; Aal, A-aligned spermatogonia; Adark,type A dark spermatogonia; Apale, type A pale spermatogonia; Apr, A-pairedspermatogonia; As, A-single spermatogonia; B, type B spermatogonia;D, diplotene; In, intermediate spermatogonia; L, leptotene; M, meioticmetaphase; P, pachytene; Pl, preleptotene; Z, zygotene. Adapted with permission from ref. 82, CC BY 4.0 (CC BY 4.0 Deed | Attribution 4.0 International | Creative Commons).

a Mouse spermatogenesis

b Human spermatogenesis

 

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Fig. 5 | Gametogenesis in humans. a, Oogenesis.All possible oocytes are produced by the time ofbirth, so that only meiotic divisions occur thereafter.b, Spermatogenesis is continuous, so that withageing the number of total chromosome replicationevents (and opportunities for errors) increases.

 

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Table 2 | WHO semen analysis lower reference limits

 

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Fig. 7 | MRI assessment of male pelvic anatomy. The MRI T2 image indicatesa hyperintensity prostatic utricle cyst (arrowhead) causing ejaculatory ductobstruction and subsequent bilateral seminal vesicle dilatation (arrows).

 

[madman]

Fig. 6 | Scrotal ultrasonography for measurement of spermatic veins. The ultrasonography images demonstrate dilated spermatic veins. A diameter (D)of >3 mm (here 4.2 mm; double-headed arrow) is diagnostic of a varicocele based on imaging criteria. The panel on the right is the grey-scale image, and the left panel shows color images representing blood flow direction (red indicates flow towards the probe and blue away from the probe, not venous versus arterial blood).

 

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Fig. 8 | Internal spermatic vein ligation. a,b, Surgical microscopic image depicting the spermatic vein before (part a) and after (part b) ligation with silk suture.

 

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Table 3 | Tools to assess the quality of life of infertile couples

 

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Normal physiology of ejaculation

Ejaculation: the Process and Characteristics From Start to Finish (2022) Matthew M. Mason · Kyle Schuppe · Alexander Weber · Aaron Gurayah · Akhil Muthigi · Ranjith Ramasamy Abstract Purpose of Review Semen analysis serves as the initial step in the evaluation of male infertility. However...

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[madman]

TRT testicular atrophy

Hi, im 24 and was type 2 hypogonadal. Had a inexperienced Dr, currently in South America so low on options. Got told I would be infertile if I continued on trt 125mg / week. The testicular atrophy has started to worry me due to one Dr.'s comments on my risk on fertility. Further listening to his...

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