Nordic Centre for Fertility Preservation

A joint effort by experts (scientists and clinicians) in the Nordic countries to create a network of excellence with the aim to preserve future fertility and hormonal function in young boys with disorders threatening testicular function.

NORDFERTIL was founded in 2012 by a group of clinicians and scientists from across the Nordic countries. To date we have participating centres in Sweden, Finland, Iceland, Norway, Denmark, Estonia, Latvia and Lithuania.

Our aim is to develop procedures to preserve the future fertility and hormone function of young boys who are undergoing treatments or have disorders that may affect their long-term fertility

In addition to our research activities, we aim to train the next generation of young researchers through annual meetings and seminars as well as provide the most up-to-date information for researchers, patients and their families.

What we do

What is fertility preservation?

Fertility preservation is the process of saving or protecting germ cells (eggs or sperm) so that a person can use them to have biological children in the future.

Why is fertility preservation important

Certain types of cancer treatment, including chemotherapy or radiotherapy, can cause infertility. This is because the drugs or radiation that are used to target the fast-growing cancer cells can also target the sperm-producing cells which are known as spermatogonial stem cells. The infertility may be temporary or permanent and depends on the type and dose of cancer treatment you have received and your age. Cancer treatments are becoming more effective which means the rates of cancer survival are increasing leading to more focus on the potential side-effects of treatment such as infertility. While there are fertility preservation options available for some patients, for others, including young boys, there are no such options. This is why fertility preservation projects such as NORDFERTIL and their continued research are so important.

How does fertility preservation work?

Currently available methods for male fertility preservation focus on the cryopreservation (freezing) of sperm or testis tissue. For those who can produce a viable sperm sample, sperm freezing is the most effective method of preserving fertility. For individuals do not produce viable sperm in their ejaculate, for example those with azoospermia or young people who are unable to produce an ejaculate, testicular tissue freezing is an alternative approach. This is known as testicular tissue cryopreservation. Below we have summarised the different approaches for fertility preservation in males with a focus on young boys. We have included methods that are currently established in the clinics and those that are still undergoing research.

FAQ

In addition to the research performed, NORDFERTIL will focus on the establishment of protocols for clinical applications. Therefore, the results obtained by evaluation of testicular biopsy material and cell culture experiments will be used to generate and/or optimize already existing protocols for clinical use in cooperation with all units included in NORDFERTIL.
The following questions will be addressed within the next years:

1. Which are the best cryopreservation protocols as regards later differentiation of early male germ cells in vitro?
2. Which are the best strategies to monitor cancer cell contamination in vitro?
3. Which are the best strategies and culture conditions for human spermatogenesis in vitro?
4. Which clinical efficacy and safety measures should be monitored?

Our research

All of our research takes place at the NORDFERTIL research lab at the Karolinska Institutet in Stockholm, Sweden. At the moment there are no clinically available methods for preserving fertility in prepubertal boys, so our research is focused on the storage and use of testis tissue from young boys. We are particularly interested in the spermatogonial stem cells in these tissues and how they can be developed into sperm. Some of the questions we are interested in answering include:

- Which are the best methods for cryopreserving testis tissue to protect the spermatogonial stem cells

- How can we monitor cancer cell contamination in cryopreserved testis tissue?

- What are the culture conditions required for human spermatogenesis in vitro?

Meet the team

To be added soon!

Recent publications

• Spermatogonia Loss Correlates with LAMA 1 Expression in Human Prepubertal Testes Stored for Fertility Preservation.Kurek M, Åkesson E, Yoshihara M, Oliver E, Cui Y, Becker M, Alves-Lopes JP, Bjarnason R, Romerius P, Sundin M, Norén Nyström U, Langenskiöld C, Vogt H, Henningsohn L, Petersen C, Söder O, Guo J, Mitchell RT, Jahnukainen K, Stukenborg JB. Cells. 2021 Jan 27;10(2):241. doi: 10.3390/cells10020241.
• Cisplatin and carboplatin result in similar gonadotoxicity in immature human testis with implications for fertility preservation in childhood cancer. Tharmalingam MD, Matilionyte G, Wallace WHB, Stukenborg JB, Jahnukainen K, Oliver E, Goriely A, Lane S, Guo J, Cairns B, Jorgensen A, Allen CM, Lopes F, Anderson RA, Spears N, Mitchell RT. BMC Med. 2020 Dec 4;18(1):374. doi: 10.1186/s12916-020-01844-y.
• Fertility Preservation in Childhood Cancer: Endocrine Activity in Prepubertal Human Testis Xenografts Exposed to a Pubertal Hormone Environment. Hutka M, Kadam P, Van Saen D, Homer NZM, Onofre J, Wallace WHB, Smith LB, Stukenborg JB, Goossens E, Mitchell RT. Cancers (Basel). 2020 Sep 30;12(10):2830. doi: 10.3390/cancers12102830.
• Fertility preservation and post-treatment pregnancies in post-pubertal cancer patients: ESMO Clinical Practice Guidelines^†. Lambertini M, Peccatori FA, Demeestere I, Amant F, Wyns C, Stukenborg JB, Paluch-Shimon S, Halaska MJ, Uzan C, Meissner J, von Wolff M, Anderson RA, Jordan K; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Ann Oncol. 2020 Dec;31(12):1664-1678. doi: 10.1016/j.annonc.2020.09.006. Epub 2020 Sep 22.
• Exogenous Gonadotrophin Stimulation Induces Partial Maturation of Human Sertoli Cells in a Testicular Xenotransplantation Model for Fertility Preservation. Hutka M, Smith LB, Goossens E, Wallace WHB, Stukenborg JB, Mitchell RT. J Clin Med. 2020 Jan 18;9(1):266. doi: 10.3390/jcm9010266.
• Rebuilding the human testis in vitro. Oliver E, Stukenborg JB.Andrology. 2020 Jul;8(4):825-834. doi: 10.1111/andr.12710. Epub 2019 Sep 28.
• Spermatogonial quantity in human prepubertal testicular tissue collected for fertility preservation prior to potentially sterilizing therapy. Stukenborg JB, Alves-Lopes JP, Kurek M, Albalushi H, Reda A, Keros V, Töhönen V, Bjarnason R, Romerius P, Sundin M, Norén Nyström U, Langenskiöld C, Vogt H, Henningsohn L, Mitchell RT, Söder O, Petersen C, Jahnukainen K. Hum Reprod. 2018 Sep 1;33(9):1677-1683. doi: 10.1093/humrep/dey240.
• Cancer treatment in childhood and testicular function: the importance of the somatic environment. Stukenborg JB, Jahnukainen K, Hutka M, Mitchell RT. Endocr Connect. 2018 Feb;7(2):R69-R87. doi: 10.1530/EC-17-0382. Epub 2018 Jan 19.
• Decreased spermatogonial quantity in prepubertal boys with leukaemia treated with alkylating agents. Poganitsch-Korhonen M, Masliukaite I, Nurmio M, Lähteenmäki P, van Wely M, van Pelt AMM, Jahnukainen K, Stukenborg JB. Leukemia. 2017 Jun;31(6):1460-1463. doi: 10.1038/leu.2017.76. Epub 2017 Mar 8.
• Establishing reference values for age-related spermatogonial quantity in prepubertal human testes: a systematic review and meta-analysis. Masliukaite I, Hagen JM, Jahnukainen K, Stukenborg JB, Repping S, van der Veen F, van Wely M, van Pelt AM. Fertil Steril. 2016 Dec;106(7):1652-1657.e2. doi: 10.1016/j.fertnstert.2016.09.002. Epub 2016 Oct 4.

Scientific board members

The scientific board consists of two NORDFERTIL members from Sweden, Finland, Norway, Lithuania, and Denmark, Estonia, Latvia and one member from Iceland and the research coordinator. The board members are active researchers and/or physicians in the field of pediatric oncology/hematology or reproductive biology/medicine.

Participating clinical units

Sweden:

1. Astrid Lindgrens barnsjukhus/Barnonkologi; Karolinska Universitetssjukhuset, Solna
2. Astrid Lindgrens barnsjukhus/Barnhematologi; Karolinska Universitetssjukhuset, Huddinge
3. Barn- och ungdomsmedicinska kliniken, Skånes Universitetssjukhus, Lund
4. Barnkliniken/Barnonkologi, Drottning Silvias barn- och ungdomssjukhus, Sahlgrenska Universitetssjukhuset, Göteborg
5. Barnonkologi, BOND, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus, Universitetssjukhuset, Linköping
6. Barnkliniken/Barnonkologi, Uppsala Akademiska sjukhuset, Barnavdelningen för blod- och tumörsjukdomar Uppsala
7. Barnkliniken/Barnonkologi, Norrlands Universitetssjukhus, Umeå
8. Reproduktionsmedicin, Karolinska Universitetssjukhuset Huddinge

Iceland:

1. Division of Hematology-Oncology, Children's Medical Center, Landspitali Reykjavik

Finland:

1. Department of Pediatrics, Tampere University Hospital
2. Department of Pediatrics, Kuopio University Hospital
3. Department of Pediatrics, Turku University Central Hospital
4. Department of Pediatrics, Oulu University Hospital
5. Children´s Hospital; Helsinki University Central Hospital

Lithuania: To be added.

Norway: To be added.

Denmark: To be added.

Estonia: To be added.

Latvia: To be added.

Funding organizations

The NORDFERTIL project is supported by the Swedish Childhood Cancer Foundation, The Swedish Research Council, The Academy of Finland, and many other granting bodies.

Research:

NORDFERTIL, Department of Women's and Children's Health, Nordfertil Research Lab Stockholm, Childhood Cancer Research Unit, Bioclinicum, J9:30, Karolinska Institutet, and Karolinska University Hospital, Visionsgatan 4, SE-17164 Solna, Sweden
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