My approach to testicular biopsies in male infertility

A. Tzankov

https://embryology.med.unsw.edu.au

gonocytes migrate from the yolk sack

Sertoli and Leydig cells originate from the coelomic epithelium

Sex determination

Physiology

Leydig cells with Reinke crystals

Normal histology

https://embryology.med.unsw.edu.au

Spermatozoa maturation

Meiotic correlates

http://audilab.bmed.mcgill.ca

Residual bodies

Indications for therapeutic and/or diagnostic testicular biopsies

http://link.springer.com/chapter/10.1007%2F978-3-540-92963-5_11#page-1

Techniques

• Modified Karnofsky solution

• ½ hydroxyethyl-methacrylate resin embedding

• ½ paraffin embedding

My approach • Is there a cause other than expected?

– Vasculitis?

– Amyloidosis?

– Inflammation?

– Ischemic changes?

– Microlithiasis?

– GCNIS?

If not

Was the clinician polite?

Constellation Cause Comment

T low, FSH high Problem with the Leydig and Sertoli cells e.g. Klinefelter

T low, FSH low Problem with the pituitary gland, E2 MRI, other tests

T normal, FSH high(er) Germ cell aplasia Biopsy!

T normal, FSH low T substitution, anabolic steroid ingestion Anamnesis?

T high, FSH low Androgen insensitivity Status?

All normal, but infertile Obstruction, toxicity Status? Biopsy!

If not

Is there a pattern suggestive of

– Cryptorchidism

– Tubular sclerosis

– Germ cell aplasia

– Hypospermatogenesis

– Karyotypic abnormality

– Gonadotropic deficiency

If not

Think of – Low motility problem (ElMi)

• Round head sperms

• Immotile cilia

– Excurrent duct obstruction (occ. sperm granulomas)

• Sperm counts lower than expected from the number of spermatids/canalicular cross section

• Anamnesis (surgery? vasectomy? cystic fibrosis?)

• Status (palpation! agenesis? cystic fibrosis?)

– Too much is too much

• All 16 days spermatogonia start maturational processes that last for 60 day

Patterns

Cryptorchidic

• Prepubertal-like gonads

• Occasional germ cells w/o maturation

• No Leydig cell hyperplasia

https://expertconsult.inkling.com

Sertoli cell nodule (Pick adenoma)

Tubular hyalinization/fibrosis

• Chronic orchitis

• Ischemia

– (Local) ischemia

– Chronic torsion

– Prior surgery

Germ cell aplasia = Sertoli only syndrome

• Migration defects

• Del Castillo syndrome

– Microdeletions Y(q11)

• Prepubertal FSH deficiency or E2 exposure

• Cryptorchidism

• RTX/CTX, shortly after

– FSH usually upper normal

Maturation arrest

• RTX/CTX

• Severe stress

• Postpubertal FSH deficiency

Hypospermatogenesis

• Less than 10 spermatozoa/canalicular cross section

• Heat, varicocele, hypothyroidism, T ingestion, toxins

Karyotypic abnormality

• Klinefelter, 46XXY

• De la Chapelle, 46XX

– Klinefelter with Y-loss

• Fragile X-syndrome

• GCA/H+Leydig nodules

• FSH very high

• Risk of CNS germinoma

Testis in gonadotropic deficiency

• Prepubertal

– No Leydig cells

– Aluminal tubuli

– GCH

• Postpubertal

– Leydig cell hypoplasia

– Maturation arrest

– GCH

– Hyalinization

How to report your findings?

• Grading according to Sigg (Schw. Med. Wschr. 109, 1979): – Normal

– Grade I: reduction of spermatozoa <10/tubulus

– Grade IIa: maturation arrest at spermatid level

– Grade IIb: maturation arrest at spermatocyte level

– Grade IIc: maturation arrest at spermatogone level

– Grade III: only isolated spermatogones

– Grade IV: Sertoli only

– Grade V: tubular fibrosis

ICSI not possible