Paternity after directed collection of testicular sperm for in vitro fertilization after BMT for hematological malignancies

Ignatov, Aleksey P.; Eisenberg, Manuel S.; Turek, Paul J.

doi:10.1038/bmt.2009.372

Cited by 8 publications

(6 citation statements)

References 10 publications

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“…This indicates some degree of spermatogenesis, and these men may have a chance of retrieving sperm by testicular sperm extraction for use in assisted reproduction ( 32 ). This was done successfully in one of the survivors, and together with two other case reports ( 33 , 34 ), we find this a proof of concept.…”

Section: Discussionsupporting

confidence: 75%

Childhood reproductive hormone levels after pediatric hematopoietic stem cell transplantation in relation to adult testicular function

Mathiesen

Sørensen

Ifversen

et al. 2021

Endocrine Connections

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Objectives: Longitudinal assessment of testicular function after pediatric hematopoietic stem cell transplantation (HSCT) is needed to guide clinical follow-up. We investigated dynamics in male reproductive hormones after pediatric HSCT, focusing on pubertal timing and associations with testosterone deficiency and azoospermia in adulthood. Methods: This retrospective, longitudinal study included 39 survivors median 19 years after pediatric HSCT. Serum concentrations of LH, testosterone, FSH, and inhibin B from time of HSCT, during puberty, and into adulthood were analyzed. Pubertal timing (rise in LH and testosterone) was compared to a reference cohort of 112 healthy boys. Associations between reproductive hormone levels during puberty and adult testicular function (including semen quality) were investigated. Results: Pubertal induction with testosterone was needed in 6/26 patients who were prepubertal at HSCT. In the remaining patients, pubertal timing was comparable to the reference cohort. However, 9/33 patients (without pubertal induction) developed testosterone deficiency in early adulthood, which was associated with higher LH levels from age 14–16 years. Azoospermia in adulthood was found in 18/26 patients without testosterone substitution. Higher FSH and lower inhibin B levels from mid-pubertal age were associated with azoospermia in adulthood, in patients being prepubertal at HSCT. Conclusion: Our results indicate a substantial risk of deterioration in testicular function after pediatric HSCT, despite normal pubertal timing. Although reproductive hormone levels from mid-puberty indicated adult testicular function, prolonged follow-up into adulthood is needed in these patients, including clinical examination, reproductive hormone analysis, and semen sample for patients interested in their fertility potential.

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Section: Discussionsupporting

confidence: 75%

Childhood reproductive hormone levels after pediatric hematopoietic stem cell transplantation in relation to adult testicular function

Mathiesen

Sørensen

Ifversen

et al. 2021

Endocrine Connections

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“…2 While few cases of successful conception or spermatogenic recovery after HSCT, with chemotherapy alone, or combined with TBI conditioning, have been reported 1, [3][4][5][6][7][8][9][10][11][12] (Table 1), other studies assessing male fertility after HSCT have not reported any conception, highlighting the increased risk of altered reproductive function after HSCT. In 2010, the patient was still in complete remission.…”

Section: Dear Editormentioning

confidence: 99%

Spontaneous conception after autologous hematopoietic stem cell transplantation: a case report

Dupont¹,

Bally²,

Eustache³

et al. 2012

Asian J Androl

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“…Spontaneous paternity and live birth following bone marrow conditioning and transplantation has surprised everyone. Ignatove et al [ 40 ] reviewed 8 such cases and reported two more themselves, where although the patients were azoospermic, testicular sperm helped attain biological parenthood. Dupont et al [ 41 ] recently reported spontaneous conception after autologus BMT.…”

Section: Introductionmentioning

confidence: 99%

VSELs may obviate cryobanking of gonadal tissue in cancer patients for fertility preservation

2015

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BackgroundInfertility is an undesirable side effect and gonadal tissue banking is advocated in young cancer patients who are unable to preserve embryos or gametes prior to oncotherapy to achieve biological parenthood later on. Banking gonadal tissue is challenging and protocols to mature gametes in vitro are not yet clinically established. Transplanting ovarian cortical tissue at hetero-or orthotopic sites in women and bone marrow transplantation (BMT) in both men and women has resulted in spontaneous recovery of fertility, pregnancy and live births. Various studies in humans and mice suggest that genetic origin of offspring after BMT is similar to transplanted patient and not the donor. Thus the source of oocytes/sperm which result in spontaneous pregnancies still remains contentious.FindingsVery small embryonic-like stem cells (VSELs) have been reported in adult human testis and ovary, in azoospermic testicular biopsies from survivors of childhood cancer and also in women with premature ovarian failure and menopause. VSELs survive chemotherapy because of their quiescent nature and can be detected in chemoablated mice gonads at protein and mRNA level and also by flow cytometry. Surviving VSELs spontaneously differentiate into oocyte-like structures and sperm when inhibitory factors are overcome in vitro. Transplantation of mesenchymal cells (isolated from different sources) has led to regeneration of chemoablated mouse gonads and also live births. Spermatogenesis is also restored from endogenous stem cells on inter-tubular transplantation of Sertoli cells in chemoablated mouse testis.ConclusionsEndogenous VSELs (which survive oncotherapy) can possibly regenerate non-functional gonads in cancer survivors when exposed to a healthy niche in vitro or in vivo (by way of transplanting mesenchymal cells which secrete trophic factors required for endogenous VSELs to differentiate into gametes). Presence of VSELs can also explain spontaneous pregnancies after BMT and cortical tissue transplantation (at heterotopic or orthotopic sites). This understanding once verified and accepted by the scientific community could obviate the need to remove whole ovary or testicular biopsy for cryopreservation prior to oncotherapy.

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Paternity after directed collection of testicular sperm for in vitro fertilization after BMT for hematological malignancies

Cited by 8 publications

References 10 publications

Childhood reproductive hormone levels after pediatric hematopoietic stem cell transplantation in relation to adult testicular function

Childhood reproductive hormone levels after pediatric hematopoietic stem cell transplantation in relation to adult testicular function

Spontaneous conception after autologous hematopoietic stem cell transplantation: a case report

VSELs may obviate cryobanking of gonadal tissue in cancer patients for fertility preservation

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