Downloaded 12 times
Uploaded bySujoy Dasgupta
Case Based Panel Discussion Male Infertility: Past, Present and Future
The document discusses male infertility, detailing semen analysis methods and interpretation, sperm collection techniques, and various treatment approaches depending on the severity of the conditions observed. It emphasizes the need for thorough evaluation, including hormonal investigations and the potential roles of antioxidants and surgical interventions. Additionally, it highlights the importance of genetic testing and counseling in cases of severe male subfertility and the surgical options available for obstructive azoospermia.
More Related Content
Similar to Case Based Panel Discussion Male Infertility: Past, Present and Future
![Infertility [Dr. Edmond Wong]](https://cdn.slidesharecdn.com/ss_thumbnails/infertilityedmond-140716214842-phpapp02-thumbnail.jpg?width=640&height=640&fit=bounds)
More from Sujoy Dasgupta
Case Based Panel Discussion Male Infertility: Past, Present and Future
- 1. Case Based PanelDiscussion on Male Infertility: Past, Present and Future
- 2. Semen Report 1 CollectionMethod Masturbation Total Motility 30% Abstinence 4 days Progressive Motility 16% Collection Complete Non progressive Motility 14% Volume 1.5 ml Immotile 70% Viscosity Normal Motile Sperm Count 0.54 million Liquefaction Time 45 minutes Normal Morphology 1% pH 7.6 Vitality 34% Sperm Concentration 1.2 million/ ml Round cells Nil
- 3. Semen Report 1 CollectionMethod Masturbation Total Motility 30% Abstinence 4 days Progressive Motility 16% Collection Complete Non progressive Motility 14% Volume 1.5 ml Immotile 70% Viscosity Normal Motile Sperm Count 0.54 million Liquefaction Time 45 minutes Normal Morphology 1% pH 7.6 Vitality 34% Sperm Concentration 1.2 million/ ml Round cells Nil OAT Mild/ Severe?
- 4. Male Infertility- Mildor Severe? • TMSC= Total Motile sperm count = Sperm concentration x total volume x total motility (TM) • TMSC >5/ 10/ 20 million
- 5. What next? • Straightawaydonor sperm IUI • Antioxidants for 3-6 months and repeat test • Directly ICSI with self sperms • Repeat the test ASAP and investigate in details
- 6. What next? • Straightawaydonor sperm IUI • Antioxidants for 3-6 months and repeat test • Directly ICSI with self sperms • Repeat the test ASAP and investigate in details
- 7. When to repeatsemen analysis? • Mild problems- After 3 months • Severe problems- ASAP (NICE, 2013; EUA, 2018; ASRM, 2020)
- 8. Prolonged use ofantioxidants?
- 9. I n fe r t i l i t y O X I D A N T P R O D U C T I O N A N T I O X I D A N T D E F E N C E S S Y S T E M
- 10. Severe Male Factor-if not left untreated ??? • Overall, 16 (24.6%) of 65 patients with severe oligozoospermia developed azoospermia. • Two (3.1%)patients with moderate oligozoospermia developed azoospermia • None of the patients with mild oligozoospermia developed azoospermia. Consider freezing the sperms
- 12. Smits RM, Mackenzie-ProctorR, Yazdani A, Stankiewicz MT, Jordan V, Showell MG. Antioxidants for male subfertility. Cochrane Database Syst Rev. 2019;3(3):CD007411. Published 2019 Mar 14. • may improve live birth rates • clinical pregnancy rates may also increase. • Overall, there is no evidence of increased risk of miscarriage, however antioxidants may give more mild gastrointestinal upsets • Subfertilte couples should be advised that overall, the current evidence is inconclusive.
- 13. • In somestudies, AS was found to be beneficial in reversing OS- related sperm dysfunction and improving pregnancy rates. • The most commonly used preparations, either as monotherapy or in combination as multi-AS, were: vitamin E (400 mg), carnitines (500–1000 mg), vitamin C (500–1000 mg), CoQ10 (100–300 mg), NAC (600 mg), zinc (25–400 mg), folic acid (0.5 mg), selenium (200 mg), and lycopene (6–8 mg). • Still debatable due to the heterogeneity in study designs and the multifactorial genesis of infertility.
- 14. Detailed Evaluation History andExamination Varicocele Vas derens Testicular location Darren et al. Male infertility – The other side of the equation . 2017
- 15. Ultrasound showing varicocele Advisevaricocelectomy?
- 16. Varicocele- always CLINICALDiagnosis • Subclinical: not palpable or visible, but can be shown by special tests (Doppler ultrasound). • Grade 1: palpable during Valsava manoeuvre, but not otherwise. • Grade 2: palpable at rest, but not visible. • Grade 3: visible at rest.
- 17. Surgery for Varicocele(EUA, 2018) • Grade 3 varicocele • Ipsilateral testicular atrophy • Abnormal semen parameters • No other fertility factors in the couple
- 18. In couples seekingfertility with ART, varicocele repair • may offer improvement in semen parameters • may decrease level of ART needed
- 19. Do you recommendvaricocelectomy here? • 35 yr- Azoospermia • Lt undescended testis • 19 yr age- Lt orchidopexy • 21 yr age- left testicular cancer (mixed germ cell Tx)→ orchidectomy, f/b 3 cycles of chemotherapy (BPC) • 33 yr age-Papillary Ca Thyroid→ Total thyroidectomy and neck LN dissection f/b Radio-iodine. Now on Eltroxin 150
- 20. Imaging Scrotal ultrasound 1. Clinicallyabnormal findings- mass/ atrophy 2. Tight scrotum (Cremasteric reflex) 3. Obese patient • NOT for Varicocele detection • NOT the replacement for clinical examination (EUA, 2018; ASRM/ AUA, 2020) Transrectal ultrasound (TRUS) 1. Low volume and pH of semen 2. Ejaculatory disorders (EUA, 2018; ASRM/ AUA, 2020)
- 21. “Abnormal” scrotal ultrasound Epididymalcyst Microlithiasis Testicular prosthesis
- 22.
- 23. Sperm concentration <10million/ml Sexual dysfunction Clinically suspected endocrinopathy FSH, LH, Testosterone, HbA1C FSH/ LH low Testosterone low Serum Prolactin Pituitary Imaging FSH high LH hig h Tes tost ero ne low Globa l Testic ular failure LH normal Testoste rone normal Sper mato genes is defect LH high Testoste rone normal Subcl inical hypo gona dism Prolactin, TSH if clinically suspected
- 24. Concentration 0.2 mil/ml •FSH 0.22, LH 0.34, Testo 549 • Pituitary MRI- normal • How to treat?
- 25. How to manage-Hypo-Hypo? • hCG 2000-5000 IU 3 times a week • Serum testosterone should be checked every 1–2 months • The sperm count should be monitored monthly • Sperm parameters become normal within 6 months but sometimes it can take 24 months of time • If hCG alone cannot restore spermatogenesis, FSH is added in the dose of 75-150 IU 3 times a week • Often can father the baby at much lower sperm concentration EUA, 2018; ASRM/AUA, 2020
- 26. Hormone treatment vsART • Priority for natural conception • Other indications of ART- female partners • Age of female partners/ ovarian reserve • Time to pregnancy • Cost
- 27. Stories of Hypo/Hypo •29 yr, Azoospermia • Delayed puberty • Anosmia • MRI- B/L olfactory bulb absent • Genetic tests advised, Lost to F/U. •32 yr, Azoospermia •sudden loss of body hair, low libido •Nonfunctioning Pituitary macroadenoma → Endoscopic surgery H/P Lymphocytic hypophysitis •Started hCG f/b hMG by endocrinologist •Sperm conc 1-2/ hpf • 30 yr, Azoospermia • 17 yr age, sudden testicular atrophy • B/L testes 6 cc each
- 28. After 6 months,TMSC 4 million: IUI/ IVF/ ICSI? • Assess 1. Tubal factor 2. Ovarian reserve 3. Duration of Infertility 4. Age of the female partner
- 29. Hamilton et al.,2015 Criteria TMSC Treatment Pre wash TMSC > 5 million IUI Pre wash TMSC 1 - 5 million IVF Pre wash TMSC <1 million ICSI IUI, IVF or ICSI?
- 30. TMSC <5 mil/mland IUI • Counsel before IUI 1. Double Ejaculate Kucuc et al., 2004; Oritz et al., 2016 2. “Trial IUI”- Post wash- IMSC Ombelet et al., 2014 3. IMSC >1 mil/ml → Further IUI 4. IMSC <1 mil/ml → ICSI 5. No role of double insemination or any special washing technique ESHRE, 2018 Donor sperm is NOT the only solution
- 31. Semen Report 2 CollectionMethod Masturbation Abstinence 5 days Collection Complete Volume 3.0 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 7.8 Sperm Concentration Nil (even after centrifugation) Round cells Nil
- 32. Semen Report 2 CollectionMethod Masturbation Abstinence 5 days Collection Complete Volume 3.0 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 7.8 Sperm Concentration Nil (even after cetrifugation) Round cells Nil Azoospermia
- 33. Can we guess-OA/ NOA? OA NOA Semen Volume low (<1 ml) pH low (<7) Volume normal (>1.6 ml) pH normal (>7.4) Seminal fructose Negative Positive Testicular size Normal Small Epididymis Fullness Normal/ small Vasa May not be palpable Palpable FSH Normal High Testosterone Normal May be low Chance of sperm recovery 100% 50-60%
- 34. What next? • Straightawaydonor sperm IUI • Testicular FNAC?
- 35. FNAC- role? ASRM/ AUA,2020 • Consider TESA in indeterminate cases- NOT NECESSARY FSH >7.6 <7.6 Testicular long axis <4.6 cm >4.6 cm 89% chance of NOA 96% chance of OA
- 36. Problems with indiscriminateFNAC • Repeat test showed SC 2 mil/ml Karyo- 46,XX
- 37. If previous FNACshowed unfavourable report? Diagnosis Chance of sperm retrieval by Micro TESE Sertoli-cell-only syndrome (Germ cell hypoplasia) 32% Maturation arrest 66.7% (Late MA> Early MA) Hypospermatogenesis 100% Tuberous sclerosis 33.3% Mixed atrophy 95.2% (Schwarzer, 2013)
- 38. Physical Exam • 31yr • Azoospermia • USG- Rt testis in lower abdomen, Lt testis in inguinal canal • FSH 13.40. LH 6.87. Testo 6.89. E2 <10. Was FNAC indicated here?
- 39. Orchidectomy/ Orchidopexy inadult? • In adulthood, a palpable undescended testis should NOT be removed because it still produces testosterone. • Correction of B/L cryptorchidism, even in adulthood, can lead to sperm production in previously azoospermic men • Perform testicular biopsy at the time of orchidopexy in adult- to detect germ cell neoplasia in situ EUA, 2018
- 40. B/L cryoptorchidism inADULTS!!!
- 41. Hormonal Investigations • FSH25.21 IU/L (normal 1-10) • LH 16.8 IU/L (normal 1-10) • Testosterone 159 ng/dl (normal 200-800 ) Testosterone supplementation? Any other medical therapy?
- 42. Medical Therapy inIdiopathic OAT (mostly hypergonadotrophic hypogonadism) • To improve the chance of sperm retrieval • Sometimes, can lead to appearance of sperms in the ejaculate Testosterone supplementation Strongly CONTRAINDICATED Feedback inhibition on FSH, LH→ secondary hypogonadism Aromatase inhibitors (Letrozole, Anastrozole) If T:E2 ratio <10 (T- ng/dl, E2- pg/ml) Anti-estrogens (CC, Tamoxifen) •Block pituitary E2 receptors→ stimulate secretion of FSH, LH •Men with normal FSH, low testosterone but normal T:E ratio Gonadotrophins •“resetting” of the Gn receptors in testicles → improve the sensitivity of testicles to gonadotrophins •may be increase intratesticular testosterone •work better in case of eugonadism rather than high FSH •If successful in raising FSH level 1.5 times baseline and testosterone 600-800 ng/dl, high success rate of microTESA (Alkandari and Zini, 2021; Kumar, 2021; Holtermann et al., 2022; Dabaja and Schlegel, 2014; Holtermann et al., 2022; Anawalt, 2013; Flannigan and Schlegel, 2019; Ring et al., 2016; Chehab et al, 2015; Foran et al, 2023). Shiraishi et al., 2012)
- 43. FSH Testosterone SemenDiagnosis Treatment APHRODITE Group 1 Low Low Abnormal including Azoos Hypogonadotropic hypogonadism hCG (+ FSH if needed) APHRODITE Group 2 Normal Normal (≥350 ng/dl) Abnormal including Azoos Reduced Gonadotropin action, functional hypogonadism FSH only APHRODITE Group 3 Normal Low Abnormal including Azoos Reduced Gonadotropin action, biochemical hypogonadism FSH (+hCG) APHRODITE Group 4 High Normal/ Low Abnormal including Azoos Functional hypogonadism hCG (+ FSH if needed) APHRODITE Group 5 Normal Normal (≥350 ng/dl) Normal Unexplained couple infertility ?FSH only APHRODITE Criteria, RBMO, 2024 Addressing male Patients with Hypogonadism and/or infeRtility Owing to altereD, Idiopathic TEsticular function
- 44. Can we refusesurgical sperm retrieval? • Testicular volume 6 cc each side • Serum FSH 25.21 FSH, testicular size or other markers- can NOT be used for prediction/ refusal (EUA, 2018; ASRM/AUA, 2020)
- 45. ONLY predictors ofsperm retrieval? • No reliable positive prognostic factors guarantee sperm recovery for patients with NOA • The only negative prognostic factor is the presence of AZFa and AZFb microdeletions.
- 46. • Sperm concentration<5 million/ml • Azoospermia • Testicular atrophy • Elevated FSH (EUA, 2018; ASRM/ AUA, 2020) • Karyotyping • Y chromosome Microdeletion (YMD) Genetic testing in severe male subfertility?
- 47. Y chromosome microdeletion AZFc/d SSR can be attempted AZF a/b SSR should NOT be attempted
- 48. Genetic changes- whatto do? 45, XY rob (14, 21), (q10, q10) Azoospermia Robertsonian Translocation 46,XY;t(2:22)(q37;q11.21) Severe OAT Reciprocal Translocation Genetic Counseling PGT- SR Prenatal testing
- 49. Should karyotype bedone selectively? • 37 yr • FSH 35.42, LH 10.13, testo 93, E2 14.45 • Undiagnosed Diabetes • Prev FNAC- Lt side- Sertoli Only Syndrome • TESE – Rt side- No sperms, Lt side- Motile Sperms
- 50. • 39 yr •FSH 25.4, LH 12.6, Estradiol 14, Testo 61. What to do here? 46,XX; SRY positive
- 51. Are these “geneticabnormalities”? 46,XY,15ps+ 46,X,Y,q+ 46,X,inv(Y)(p11.q11) 46,X,inv(Y)(p11.2q11.2) Keep geneticist on board
- 52. Semen Report 3 CollectionMethod Masturbation Abstinence 2 days Collection Complete Volume 0.5 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 6.8 Sperm Concentration Nil (even after centrifugation) Round cells Nil
- 53. Semen Report 3 CollectionMethod Masturbation Abstinence 2 days Collection Complete Volume 0.5 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 6.8 Sperm Concentration Nil (even after centrifugation) Round cells Nil Azoospermia
- 54. Fructose negative azoospermia Anyrole of clinical exam? Vasa palpable • Ejaculatory duct obstruction • TRUS Vasa NOT palpable • CBAVD • Why important?
- 55. Surgical Management inOA: When to refer? • Vasovasostomy • Vasoepididymostomy • Transurethral resection of ejaculatory ducts in EDO • Patent tract ≠ Conception Baker and Sabanegh, 2013
- 56. CBAVD: What next? • Semen-Volume <1.5 ml, pH <7.0, fructose negative • TRUS • Renal ultrasound • Cystic fibrosis mutation (CFTR) testing (EUA, 2018; ASRM/AUA, 2020) • Partner testing if the man is carrier • Indian prevalence- 1:10,000- 1:40,000 (Kapoor et al., 2006; Prasad et al., 2010)
- 57. Case of CBAVD-TRUS and CFTR mutation Partner testing needed Partner testing NOT needed
- 58. CBAVD is NOTuncommon • CFTR negative • CFTR carrier • Wife- normal • CFTR refused • CFTR carrier • Wife- normal • CFTR negative
- 59. Surgical Sperm Retrieval(SSR): Which method?
- 60. Indication Process MeritsDemerits PESA (percutaneous epididymal sperm aspiration) OA •minimally invasive •minimum training •“blind” method •can cause epididymal damage/ fibrosis •sufficient sperms may not be obtained for freezing MESA (microsurgical epididymal sperm aspiration) OA •higher chance of sperm recovery •full scrotal exploration •microsurgical reconstruction can be attempted •sufficient sperms obtained for freezing •invasive, expensive •needs expertise •takes time to recover TESA (testicular sperm aspiration) NOA OA •minimally invasive •minimum training •“blind” method •sufficient sperms may not be obtained for freezing TESE (testicular sperm extraction) NOA OA •higher chance of sperm recovery •sufficient sperms obtained for freezing •invasive, expensive •can cause testicular fibrosis/ damage •needs expertise •takes time to recover MicroTESE NOA OA •highest chance of sperm recovery •sufficient sperms obtained for freezing •invasive, expensive •needs expertise (Tournaye et al., 2018; Fritz and Speroff, 2011; Coward and Mills, 2017).
- 61. Semen Report 4 CollectionMethod Masturbation Total Motility 58% Abstinence 4 days Progressive Motility 35% Collection Complete Non progressive Motility 23% Volume 2 ml Immotile 52% Viscosity Normal Motile Sperm Count 25.52 million Liquefaction Time 45 minutes Normal Morphology 5% pH 7.6 Vitality 62% Sperm Concentration 22 million/ ml Pus cells 10-15%
- 62. Semen Report 4 CollectionMethod Masturbation Total Motility 58% Abstinence 4 days Progressive Motility 35% Collection Complete Non progressive Motility 23% Volume 2 ml Immotile 52% Viscosity Normal Motile Sperm Count 25.52 million Liquefaction Time 45 minutes Normal Morphology 5% pH 7.6 Vitality 62% Sperm Concentration 22 million/ ml Pus cells 10-15% Leukocytospermia
- 63. What to do? •Antibiotics? • Culture? • Anything else?
- 64. MAGI (Male AccessoryGland Infection) • The clinical significance of an increased concentration of leukocytes in the ejaculate is controversial. • Special Tests- Round cells vs Pus cells • Method of collection • Hand washing before collection • Culture of semen • Antibiotics- only when documented infections • Look for phimosis • Consider prostatic fluid culture EUA, 2018; ASRM, 2020; Vignera et al., J Med Microbiology, 2014
- 65. “Pus Cells” andART outcome
- 66. Collection Method MasturbationAbstinence 4 days Collection Complete Volume 2 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 7.6 Sperm Concentration 36 million/ ml Total Motility 46% Progressive Motility 33% Non progressive Motility 13% Immotile 54% Motile Sperm Count 16.56 million/ ml TMSC 33.12 million Normal Morphology 5% Abnormal Morphology 95% Vitality 32% Round cells Nil • Treated for “male factor” with antioxidants • Unexplained subfertility • Conceived naturally, delivered A silly question?
- 67. Reliance of Semen“Reference Range”
- 68. Limitations of WHOSemen Analysis Guideline • 5 percentile and time-to-pregnancy (TTP) concept • Not true reference values but recommends acceptable levels. • Day to day variation • Functional ability of the sperms?
- 69.
- 70. Treatment options forhigh DFI (Agarwal et al., World J Mens Health. 2020) • ICSI with TESA • MACS, IMSI • Varicocelectomy • Treat infection • Control weight, diabetes • Quit smoking • Antioxidants • Frequent ejaculation
- 71. SDF Testing Indications Infertile menwith: • Repeated IUI or IVF failure • Recurrent spontaneous miscarriages (ESHRE, 2018) • Previous low fertilization, cleavage or blastulation rate • Varicocele with normozoospermia • Advanced male age (>40 y) Significance of SDF • Live birth after IUI/ IVF/ ICSI- ? • Oocytes can repair the damaged DNA • Lack of standardization • Lack of definitive treatment Should not be routine (ASRM, 2020; ESHRE, 2023)
- 72. What is yourdiagnosis here? • Delayed puberty • Testo 100.86. FSH 28.33. LH 13.65. E2 27.83 • Testosterone injection started at puberty - sec sex charac, voice, genital size improved • MRI pitutary microadenoma • GH, TSH, Cortisol, PRL, - all normal Karyo- 47,XXY Pituitary Incidentaloma
- 73. Semen analysis Mild problemSevere problem 1. Lifestyle changes 2. Antioxidants 1. History 2. Physical Exam 3. Repeat semen ASAP 4. Hormonal evaluation Low FSH, LH Pituitary imaging hCG/ FSH supplementation High FSH Karyotype YCM ICSI TESA for azoospermia Donor sperms Repeat semen after 3 months Normal hormones Cannot afford ICSI No sperms in TESA S/O obstruction Idiopathic Obstructive Azoo TRUS CFTR test for CBAVD Pituitary failure Testicular failure
- 74. Treatment burden forMALE infertility falls on FEMALE Thank you