Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

Microdissection testicular sperm extraction after pediatric allogeneic hematopoietic stem cell transplantation: a case series

Bone Marrow Transplantation volume 59, pages 274–277 (2024)Cite this article

Subjects

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for children with life-threatening hematological diseases, but the procedure comprises a high risk of infertility. We have previously shown that two-thirds of male survivors had azoospermia median 18 years after pediatric HSCT [1]. However, some patients with azoospermia may produce sperm that do not reach the ejaculate, giving hope for biological paternity. Microdissection testicular sperm extraction (mTESE) is a surgical procedure for men with non-obstructive azoospermia [2]. During mTESE, the testicular tissue is systematically examined using an operating microscope to identify dilated seminiferous tubules that may contain active sperm production. Biopsies from such areas are examined for the presence of mature spermatozoa that, if found, are cryopreserved for assisted reproduction. mTESE is not routinely offered to men with azoospermia after HSCT, and the literature is, to our knowledge, limited to 15 case reports worldwide [3,4,5]. Here we present a case series of five male survivors of pediatric allogeneic HSCT who, due to their wish of biological paternity, underwent mTESE for the purpose of future assisted reproduction.

Case I was transplanted for thalassemia major at age 14.1 years using a matched sibling donor and a conditioning regimen of busulfan (12.8 mg/kg, i.v.) and cyclophosphamide (200 mg/kg). A semen sample at age 19 years revealed few immotile spermatozoa, which were cryopreserved, but later deemed useless for assisted reproduction. Five following semen samples revealed azoospermia. At follow-up, he had developed type 2 diabetes mellitus but was otherwise healthy and without chronic graft-versus-host disease (GvHD). Testicular volumes were small (Table 1) and reproductive hormones indicated absent/reduced sperm production (high serum follicle stimulating hormone (FSH), low inhibin B) and Leydig cell failure (serum luteinizing hormone (LH) at upper limit of normal, low serum testosterone) (Fig. 1). Nevertheless, sperm were retrieved by mTESE (few non-progressive motile spermatozoa).

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Serum reproductive hormone levels prior to mTESE (time 0) and 3, 6, and 12 months after mTESE.

References

  1. Mathiesen S, Sørensen K, Nielsen MM, Suominen A, Ifversen M, Grell K, et al. Male gonadal function after allogeneic hematopoietic stem cell transplantation in childhood: a cross-sectional, population-based study. Biol Blood Marrow Transplant. 2020;26:1635–45.

    Article  CAS  PubMed  Google Scholar 

  2. Schlegel PN. Testicular sperm extraction: microdissection improves sperm yield with minimal tissue excision. Hum Reprod. 1999;14:131–5.

    Article  CAS  PubMed  Google Scholar 

  3. Shin T, Kobayashi T, Shimomura Y, Iwahata T, Suzuki K, Tanaka T, et al. Microdissection testicular sperm extraction in Japanese patients with persistent azoospermia after chemotherapy. Int J Clin Oncol. 2016;21:1167–71.

    Article  CAS  PubMed  Google Scholar 

  4. Ignatov AP, Eisenberg MS, Turek PJ. Paternity after directed collection of testicular sperm for in vitro fertilization after BMT for hematological malignancies. Bone Marrow Transplant. 2010;45:1474–6.

    Article  CAS  PubMed  Google Scholar 

  5. Jacobsen FM, Fode M, Sønksen J, Ohl DA, Jensen CFS. Successful extraction of sperm cells after autologous bone marrow transplant: a case report. Scand J Urol. 2019;53:174–5.

    Article  PubMed  Google Scholar 

  6. Chan PTK, Palermo GD, Veeck LL, Rosenwaks Z, Schlegel PN. Testicular sperm extraction combined with intracytoplasmic sperm injection in the treatment of men with persistent azoospermia postchemotherapy. Cancer. 2001;92:1632–7.

    Article  CAS  PubMed  Google Scholar 

  7. Hsiao W, Stahl PJ, Osterberg EC, Nejat E, Palermo GD, Rosenwaks Z, et al. Successful treatment of postchemotherapy azoospermia with microsurgical testicular sperm extraction: the weill cornell experience. J Clin Oncol. 2011;29:1607–11.

    Article  PubMed  Google Scholar 

  8. Arshad MA, Majzoub A, Esteves SC. Predictors of surgical sperm retrieval in non-obstructive azoospermia: summary of current literature. Int Urol Nephrol. 2020;52:2015–38.

    Article  PubMed  Google Scholar 

  9. Anserini P, Chiodi S, Spinelli S, Costa M, Conte N, Copello F, et al. Semen analysis following allogeneic bone marrow transplantation. Additional data for evidence-based counselling. Bone Marrow Transplant. 2002;30:447–51.

    Article  CAS  PubMed  Google Scholar 

  10. Taneja S, Rao A, Nussey S, Leiper A. Leydig cell failure with testicular radiation doses <20Gy: the clinical effects of total body irradiation conditioned haematopoietic stem cell transplantation for childhood leukaemia during long‐term follow‐up. Clin Endocrinol. 2019;91:624–32.

    Article  CAS  Google Scholar 

  11. Eliveld J, van Wely M, Meicßner A, Repping S, van der Veen F, van Pelt AMM. The risk of TESE-induced hypogonadism: a systematic review and meta-analysis. Hum Reprod Update. 2018;24:442–54.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Salooja N, Szydlo RM, Socie G, Rio B, Chatterjee R, Ljungman P, et al. Pregnancy outcomes after peripheral blood or bone marrow transplantation: a retrospective survey. Lancet. 2001;358:271–6.

    Article  CAS  PubMed  Google Scholar 

  13. Winther JF, Boice JD, Christensen J, Frederiksen K, Mulvihill JJ, Stovall M, et al. Hospitalizations among children of survivors of childhood and adolescent cancer: a population-based cohort study. Int J Cancer. 2010;127:2879–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sankila R, Olsen JH, Anderson H, Garwicz S, Glattre E, Hertz H, et al. Risk of cancer among offspring of childhood-cancer survivors. N Engl J Med. 1998;338:1339–44.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was funded by unrestricted grants from The Danish Childhood Cancer Foundation and C.C. Klestrup og hustru Henriette Klestrup’s mindelegat.

Author information

Author notes

  1. These authors contributed equally: Sidsel Mathiesen, Christian Fuglesang S. Jensen.

Authors and Affiliations

  1. Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark

    Sidsel Mathiesen & Klaus Müller

  2. Department of Urology, Copenhagen University Hospital – Herlev and Gentofte, Copenhagen, Denmark

    Christian Fuglesang S. Jensen & Jens Sønksen

  3. Department of Clinical Genetics, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark

    Anna Byrjalsen

  4. Department of Growth and Reproduction and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark

    Lise Aksglaede & Niels Jørgensen

  5. Department of Urology, University of Michigan, Ann Arbor, MI, USA

    Dana Ohl

  6. Institute for Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

    Jens Sønksen & Klaus Müller

Authors
  1. Sidsel Mathiesen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christian Fuglesang S. Jensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anna Byrjalsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lise Aksglaede
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Niels Jørgensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dana Ohl
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jens Sønksen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Klaus Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SM, CFSJ, DO, LA, NJ, JS, and KM contributed to the study design. SM, CFSJ, JS, LA, and AB collected the data. All authors contributed to the data analyses and interpretation. SM and CFSJ drafted the manuscript. All authors critically revised the manuscript and approved the final version.

Corresponding author

Correspondence to Sidsel Mathiesen.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mathiesen, S., Jensen, C.F.S., Byrjalsen, A. et al. Microdissection testicular sperm extraction after pediatric allogeneic hematopoietic stem cell transplantation: a case series. Bone Marrow Transplant 59, 274–277 (2024). https://doi.org/10.1038/s41409-023-02152-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-023-02152-8

Search

Advanced search

Quick links