Aleksander Giwercman

Fertility restoration using autologous testicular tissue transplantation is relevant for infertile men surviving from childhood cancer and, possibly, in men with absent or incomplete spermatogenesis resulting in the lack of spermatozoa in the ejaculate (non-obstructive azoospermia, NOA). Currently, testicular tissue from pre-pubertal boys extracted before treatment with gonadotoxic cancer therapy can be cryopreserved with good survival of spermatogonial stem cells. However, strategies for fertility restoration, after successful cancer treatment, are still experimental and no clinical methods have yet been developed. Similarly, no clinically available treatments can help men with NOA to become biological fathers after failed attempts of testicular surgical sperm retrieval. We present a case of a 31-year-old man with NOA who had three pieces of testis tissue (each ∼2 × 4 × 2 mm3) extracted and cryopreserved in relation to performing microdissection testicular sperm extraction (mTESE). Approximately 2 years after mTESE, the thawed tissue pieces were engrafted in surgically created pockets bilaterally under the scrotal skin. Follow-up was performed after 2, 4, and 6 months with assessment of reproductive hormones and ultrasound of the scrotum. After 6 months, all engrafted tissue was extracted and microscopically analyzed for the presence of spermatozoa. Furthermore, parts of the extracted tissue were analyzed histologically and by immunohistochemical analysis. Active blood flow in the engrafted tissue was demonstrated by doppler ultrasound after 6 months. No spermatozoa were found in the extracted tissue. Histological and immunohistochemical analysis demonstrated graft survival with intact clear tubules and normal cell organization. Sertoli cells and spermatocytes with normal morphology were located near the basement membrane. MAGE-A and VASA positive spermatogonia/spermatocytes were detected together with SOX9 positive Sertoli cells. Spermatocytes and/or Sertoli cells positive for γH2AX was also detected. In summary, following autologous grafting of frozen-thawed testis tissue under the scrotal skin in a man with NOA, we demonstrated graft survival after 6 months. No mature spermatozoa were detected; however, this is likely due to the pre-existing spermatogenic failure.

Background Growing evidence suggests intergenerational effects of paternal pre‐conceptional smoking through the germ line, but its specific impact on offspring semen quality remains uncertain because of challenges in isolating paternal exposure from maternal passive smoking or underreporting. Methods We reran previous analyses estimating differences in semen parameters and testicular size according to paternal smoking in 867 young adult men, adding first‐trimester maternal plasma cotinine to the original adjustment for maternal self‐reported smoking. We also estimated differences in sperm DNA fragmentation. Paternal smoking was reported by the pregnant women around gestational week 16. Analyses were additionally adjusted for household occupational status, parental ages at birth, maternal pre‐pregnancy body mass index and alcohol consumption, and abstinence time, and accounted for spillage, minutes from ejaculation to analysis, and son's own smoking. Results We found no association between paternal preconceptional smoking and any of the semen parameters or testicular size. Adjustment for son's own smoking did not change results. Discussion While maternal plasma cotinine offers an objective measure of tobacco exposure and allows for a more thorough adjustment of maternal smoking, the high correlation between paternal pre‐conceptional smoking and maternal cotinine exposure may, have resulted in overadjustment removing some paternal effect. Inability to distinguish between paternal never smokers and former smokers, may have led to misclassification of paternal pre‐conceptional smoking and underestimation of associations. Conclusion We found no support for an independent association between paternal pre‐conceptional smoking and semen quality in young adult sons, but studies with more detailed paternal smoking history are needed before firm conclusions can be drawn.

Data regarding excretion of SARS-CoV-2 in semen are inconclusive and counseling regarding risk of sexual transmission is still challenging. Our knowledge on the effect of upper respiratory tract infections (URTI) on male reproductive system is also scarce. Apart from negative effect of fever on spermatogenesis virtually no study has been able to compare reproductive parameters in men with COVID-19 or other URTI with predisease data. Eleven men who developed symptoms of URTI during the first and second wave of COVID-19 pandemic and who had preexistent fertility and hormonal data, participated in the study leaving sperm and blood samples. Three additional subjects were recruited among proven SARS-CoV-2 positive male hospital workers (without previous data). SARS-CoV-2 RNA was present in the ejaculate from 2 of 5 (40%) young men with mild COVID-19. In one of them viral particles could be detected in the semen sample 2 weeks after the first sampling. Men with any URTI showed higher LH ( p = 0.02 ), lower sperm concentration ( p = 0.047 ), and free testosterone ( p = 0.008 ) when compared to their samples delivered 10 years earlier. When SARS-CoV-2 positive subjects were compared to subjects with other URTIs, no difference in levels of reproductive parameters or inflammatory markers was seen. In conclusion, SARS-CoV-2 RNA can be present in the ejaculate but does not seem to affect reproductive parameters any more than other viruses. However, mild URTI was shown to affect the sperm concentration, LH, and free testosterone negatively.

STUDY QUESTION How does a history of cancer affect the likelihood of using assisted reproduction in order to achieve paternity? SUMMARY ANSWER As compared to men with no history of cancer, use of assisted reproduction to achieve paternity was more frequent in fathers with a history of cancer, mainly those with testicular, prostate, and hematological and lymphatic malignancies. WHAT IS KNOWN ALREADY Although it is well known that different types of cancer and their treatment may have a negative impact on fertility, there is a lack of data regarding the use of IVF and ICSI among male cancer survivors. STUDY DESIGN, SIZE, DURATION In this population-based nation-wide study using the Swedish Medical Birth Register, we identified all men who fathered their first-born child in Sweden between 1994 and 2014. Using personal identification numbers, anonymized data from the Swedish National Quality of Assisted Reproduction Register, Swedish Cancer Register, Swedish Multi-generation Register, and Swedish Education Register were linked with the Swedish Medical Birth Register. PARTICIPANTS/MATERIALS, SETTING, METHODS During the study period, a total of 1 181 488 men fathering their first-born child were identified. Of these, 26 901 fathers had a cancer diagnosis. Fathers diagnosed with cancer with <12 months from offspring conception, or with a cancer diagnosis after offspring conception, were excluded (n = 21 529). The remaining fathers who had a history of cancer (n = 5372) were divided into three groups based on age at cancer diagnosis (<15, ≥15 and <24, or ≥24 years). For subgroup analyses, they were also grouped according to the cancer location using ICD-7 codes. The fathers with no cancer diagnosis (n = 1 154 587), were included as controls. In total, 1 159 959 men were included. Associations between IVF/ICSI use and history of cancer were evaluated using logistic regression models, unadjusted and adjusted for paternal education, fathers age at childbirth, and year of conception, yielding crude and adjusted odds ratio (aOR), respectively, with a 95% CI. MAIN RESULTS AND THE ROLE OF CHANCE As compared to controls, childhood cancer survivors were only more likely to achieve paternity through ICSI (aOR 3.52, 95% CI 2.52–4.93; P < 0.001) but not through IVF treatment (aOR 1.02, 95% CI 0.61–1.70; P = 0.955). Similarly, teenage and young adult cancer survivors were more likely to father through ICSI treatment (aOR 6.84, 95% CI 5.64–8.30; P < 0.001) but not using IVF (aOR 1.27, 95% CI 0.90–1.80; P = 0.17). However, adult cancer survivors were more likely to conceive through either ICSI (aOR 5.52, 95% CI 4.86–6.27; P < 0.001) or IVF treatment (aOR 1.32, 95% CI 1.09–1.60; P = 0.004). In subgroup analyses, childhood survivors of testicular cancer (aOR 5.15, 95% CI 1.20–22.0; P = 0.027), soft tissue and bone cancers (aOR 4.70, 2.13–10.4; P < 0.001), hematological and lymphatic cancers (aOR 4.49, 95% CI 2.72–7.40; P < 0.001), or central nervous system (CNS) and eye cancers (aOR 2.64, 95% CI 1.23–5.67; P = 0.012), were at an increased likelihood of fathering through ICSI. Teenage and young adult survivors of testicular canc