MALE INFERTILITY

WYCKMELL OCTOF INGRATOEBOEN

DEPARTMENT OF UROLOGY
FACULTY OF MEDICINE UNIVERSITAS INDONESIA
DR. CIPTO MANGUNKUSUMO HOSPITAL
INTRODUCTION

Definition
Primary
 The inability of a sexually active, non-contracepting couple to achieve spontaneous pregnancy in one year.

Secondary
 Couples who have been able to get pregnant at least once, but now are unable

Epidemiology
 15% couple don’t achieve pregnancy in one year and seek medical treatment for infertility
 50% of couples due to male infertility associated by abnormal semen parameters
MALE REPRODUCTION SYSTEM

CENTRAL
 Hypothalamus
 Hypofisis

PERIFER
 Testicle
 Epididymis
 Seminal Vesicle
 Ejaculatory Duct
 Prostate
 Penis
HORMONAL REGULATION
ETIOLOGY OF INFERTILITY

Pre-testicle
 Problems in producing hormones for sperm production

Testicle
 Infection
 Varicocele
 Drugs

Post-testicle
 Blockage of sperm transport
  Absences of vas deferens
  Vasectomy
  Prostate, infection
 Erection and ejaculation problems
ETIOLOGY OF INFERTILITY

Male fertility can be impaired as a result of

 Congenital or acquired urogenital abnormalities
 Malignancies
 Urogenital tract infections
 Increased scrotal temperature (e.g. as a consequence of varicocele)
 Endocrine disturbances
 Genetic abnormalities
 Immunological factors
  In 30-40% of cases: IDIOPATHIC
EAU 2019 RECOMMENDATIONS
PROGNOSTIC FACTORS

 Duration of infertility

 Primary or secondary infertility

 Results of semen analysis

 Age and fertility status of female partner

  the fertility potential of a woman aged
  35 years  50%
  38 years  25% at 38 years, 5% at
  > 40 years  < 5%
ROLE OF UROLOGY IN MALE INFERTILITY

DIGNOSIS
 Anamnesis
 Physical Examination
 Additional Examination

TREATMENT
 Medical (hormonal and roborantia)
 Surgery
DIAGNOSTIC EVALUATION

Semen analysis
 If the results are normal  one test is sufficient.
 If the results are abnormal in at least two tests
 further andrological investigation

oligozoospermia: < 15 million spermatozoa/mL

asthenozoospermia: < 32% progressive motile spermatozoa
teratozoospermia: < 4% normal forms

OAT spermatozoa < 1 million/mL

 obstruction of the male genital tract
 Genetic abnormalities
DIAGNOSTIC EVALUATION

Hormonal Test
DIAGNOSTIC EVALUATION

Scrotal Ultrasound
 Detail anatomy of epididymis and testis
 Varicocele or sign of obstruction
DIAGNOSTIC EVALUATION

Additional Assessment

 Urinalysis
 Post-ejaculation Urinalysis
 Seminal Leukocyte Analysis
 Venography
 Anti-sperm antibody assessment
 Trans-rectal Ultrasound
 Hypo-osmotic swelling test
 CT-Scan
 Sperm Penetration Assay
 MRI
 Sperm-cervical mucus interaction
 Testicle Biopsy
 Chromosomal analysis
 Vasography
 Semen culture
EAU 2019 RECOMMENDATIONS
TREATMENT

 Pre Testicular

 Testicular

 Post Testicular
PRE TESTICULAR: GENETIC DISORDER

Chromosomal abnormalities
 Sex chromosome abnormalities (e.g. klinefelter’s syndrome)
 Autosomal abnormalities
 Sperm chromosomal abnormalities

Genetic defects
 Kallmann’s syndrome  hypogonadotropic hypogonadism
 Mild Androgen Insensitivity syndrome
 Other X-disorder

Y microdeletions

Cistic Fibrosis  Congenital bilateral absence of the vas deferens (CBAVD)

PRE TESTICULAR: GENETIC DISORDER

Therapy
 ICSI (intracytoplasmic sperm injection)
 Genetic counseling
EAU 2019 RECOMMENDATIONS
PRE TESTICULAR: HYPOGONADOTROPIC-HYPOGANADISM

Clinical condition
 FSH Low
 LH Low
 Testosterone Low
 Prolactine Normal

Therapy
 FSH Recombinant
 GnRH Stimulation
PRE TESTICULAR: HYPOGONADOTROPIC-HYPOGANADISM

Human Chorionic Gonadotropin

 Succesful rate : 22-69% based on semen improvement
 Initiated at 1,000 IU IM or SC
  every other day to normalize serum testosterone concentration
 Side effect : Gynecomastia

Pulsatile GnRH
 SC administration of GnRH in a pulsatile manner through a portable pump
  delivers a GnRH bolus every two hours
 Can induce spermatogenesis in approximately 90%-95% of men with HH
PRE TESTICULAR: HYPERGONADOTROPIC-HYPOGANADISM

Clinical condition
 FSH High
 LH High
 Testosterone Normal/Low
 Prolactine Normal

 Sign of Testicular failure  biopsy or sperm retrieval

PRE TESTICULAR: HYPERGONADOTROPIC-HYPOGANADISM

Testicular biopsy
 Can be part of ICSI treatment
  patients with clinical evidence of NOA
  testicular sperm extraction (TESE), microsurgical TESE

 The results of ICSI

  NOA < ejaculated semen and OA
  Birth rates are lower in NOA vs OA (19% vs 28%)
PRE TESTICULAR: HYPERPROLACTINEMIA

Clinical condition
 FSH Normal/Low
 LH Normal/Low
 Testosterone Low
 Prolactine High

Therapy
 Dopamine Agonist: Bromocriptine mesylate
TESTICULAR: TESTICULAR DEFICIENCY

Therapy
• TEFNA
• TESE
• ICSI
 Causes of testicular deficiency
TESTICULAR: VARICOCELE

Incidence
 Physical abnormality present in 11% of adult males
 25% of those with abnormal semen analysis

Classification
 Subclinical
 Grade 1 Palpable during straining
 Grade 2 Palpable without straining
 Grade 3 observe
TESTICULAR: VARICOCELE

Treatment

Embolization
 Antegrade Sclerotherapy
 Retrograde Sclerotherapy
 Retrograde embolization

Surgery
 Inguinal Approach
 High ligation
 Microsurgery
 Laparascopy
TESTICULAR: CRYPTORCHIDISM/UDT

Incidence
 2-5 % of the new born baby
 Caucacian > African-Americans
 Premature babies >> full-term babies
 Decrease after 3 month

Relationship with fertility

 Unilateral: paternity is independent of age at orchidopexy, and preoperative testicular location and testicular size
 Bilateral: the rate of paternity is only 35 - 53%
TESTICULAR: CRYPTORCHIDISM/UDT

Therapy
Hormonal
 hCG / GnRH → no longer recommended

Surgical
 Orchidopexy
  The success rate 70-90%
OAT SYNDROME
Consist of
 Oligozoospermia
 Asthenozoospermia
 Teratozoospermia
Incidence
 44% of all infertile men

Therapy
 Androgens, hCG/human menopausal gonadotropin, bromocriptine, α-blockers, systemic corticosteroids and magnesium supplementation
  Not effective
 FSH and anti-estrogens in combination with testosterone
  might be beneficial in a selection of patients
 Need further studies
POST TESTICULAR : OBSTRUCTIVE AZOOSPERMIA
POST TESTICULAR : OBSTRUCTIVE AZOOSPERMIA

Classification and treatment

 Intra-testicular obstruction
  TESE/TEFNA + ICSI

 Epididymal obstruction  Ejaculatory ducts obstruction

  MESA + ICSI   TURED

 Vas deferens obstruction  Function obstruction of distal seminal ducts

  Vaso-vasostomy/vaso-epididimostomy   Antegrade seminal tract washout
  TESE/MESA + ICSI
SPERM RETRIEVAL TECHNIQUE
TESE (TESTICULAR SPERM EXTRACTION)

Indication
 Non Obstructive Azoospermia

Pregnancy rate
 43%  when combined with ICSI
MICROSURGICAL EPIDIDYMAL SPERM ASPIRATION (MESA)

Indication
 Congenital Aplasia of the vas deferens (CBAVD)
 In-operable obstruction of the seminal pathways
 Ejaculatory disorders
  conservative therapy has not been successful
 Failed vaso-vasostomy

Pregnancy rate
 14 – 66 %  when combined MESA-ICSI

Sperm retrieval rate

 94% on all men with obstructed azoospermia
INTRA CYTOPLASMIC SPERM INJECTION (ICSI)

Indication
 Men with surgically unreconstructible obstruction
 Men with few viable sperm in the ejaculate
 Azoospermic men with varicoceles
 Men with nonobstructive azoospermia
 Fertilisation with immature sperm forms

Pregnancy rate
 26-57%
TRANS URETHRAL RESECTION OF THE EJACULATORY DUCTS

Indication
 Ejaculatory duct obstruction
  Low ejaculate volume with azospermia

Pregnancy rate
 25%
VASO-EPIDIDYMOSTOMY

Indication
 Congenital
 Infectious
 Post vasectomy
 Idiopathic epididymal obstruction

Pregnancy rate
 20-40%  through intercourse

Patency rate after vasectomy <3 years

 97%  pregnancy rate 76%

Patency rate after vasectomy 15 years

 71%  pregnancy rate 30%
CONCLUSION

 Infertility affected 50% with abnormal semen findings

 Various etiology of Infertility has been discovered

 Fertility-assisted technology
  widely treated the infertile couple with various pregnancy rate

 Hormonal therapy may have role on hypogonadotrophic-hypogonadysm

 Genetic testing and counseling is needed prior of ICSI

TERIMA KASIH
 NOTULENSI DISKUSI DAN TANYA JAWAB
SELASA, 21 APRIL 2020 INFERTILITAS
KONSULEN: DR. PONCO BIROWO, SP.U(K), PHD

Pertanyaan 1. Kapan diperiksa analisis genetik pada pasien infertilitas?

Pada pasien azoospermia dan severe oligospermia

Pertanyaan 2. Pada pasien orchidektomi unilateral, berapa persen penurunan mengalami infertilitas?
50-57% konsentrasi sperma berkurang dari 15 juta

Pertanyaan 3. Pasien dengan azoospermia apakah harus dengan vasography untuk menentukan obstruktif?
Prinsipnya tidak mengerjakan vasografi karena dapat menyebabkan obstruksi. Pemeriksaan yg dilakukan
adalah: - Volume testis - Hormon - Biopsi mapping sebelum sperm retrieval
 NOTULENSI DISKUSI DAN TANYA JAWAB
SELASA, 21 APRIL 2020 INFERTILITAS
KONSULEN: DR. PONCO BIROWO, SP.U(K), PHD
Pertanyaan 4. Apakah ada tempatnya dilakukan mikroligasi varikokel terlebih dahulu sebelum PESA/TESE?
Awalnya: mikroligasi varikokelektomi Selanjutnya: MESA/TESE + ICSI

Pertanyaan 5. Kapan dilakukan sperm retrieval pada pasien dengan post ligasi varicocele?
3 bulan setelahnya

Pertanyaan 6. Apakah diperlukan halo test (DNA fragmentation) pada normospermia?

Perlu

Pertanyaan 7. Pada OAT apakah dapat diberikan testosteron? Pasien seperti apa?
Saat ini, tidak ada tempatnya diberikan testosteron
 NOTULENSI DISKUSI DAN TANYA JAWAB
SELASA, 21 APRIL 2020 INFERTILITAS
KONSULEN: DR. PONCO BIROWO, SP.U(K), PHD
Pertanyaan 8. Apakah varicocle subclinis perlu diintervensi?
Varikokel subclinical dan sperma normal = tidak dioperasi
Bila varikokel clinical dan subclinical bilateral = operasi

Pertanyaan 9. Kemungkinan fertilitas post varicoclectomy?

Setelah pasien dilakukan repair varicocle, kemungkinan meningkatkan fertilitas 60%
pada pasien yang dilakukan PESA/TESE, kmungkinan ditemukan sperma 40%

Pertanyaan 10. Peran roboransia pada OAT idiopatik apakah masih ada tempatnya?
Angka keberhasilan 20-30% bila diberikan roboransia
 NOTULENSI DISKUSI DAN TANYA JAWAB
SELASA, 21 APRIL 2020 INFERTILITAS
KONSULEN: DR. PONCO BIROWO, SP.U(K), PHD

Pertanyaan 11. Bila pasien azoospermia, dilakukan MESA biopsi, terus Johnson score nya tinggi, bagaimana
selanjutnya?
Cek lihat hormonnya, bila etiologi hipo hipo bisa dikasih hormonal therapy. Bila ada varikokel, perbaiki dulu
varikokelnya. Pasien SCOS hanya <10% berhasil buat MESA/TESE berikutnya ketemu sperma

Pertanyaan 12. Kapan LH wajib kita periksa?

Lengkap periksa semua dan rutin: FSH LH Testosteron, tetapi kalau hanya pilih 2 hanya FSH dan Testosteron