Natural pregnancy following kidney transplantation in an azoospermic male: a case report

Introduction

Chronic kidney disease (CKD) is characterized by ongoing irregularities in kidney structure, function, or imaging, or a glomerular filtration rate (GFR) below 60 mL/min for at least 3 months (1,2). CKD is linked to reduced fertility in both men and women, primarily due to the escalating disruptions of the hypothalamic-pituitary-gonadal (HPG) axis (3-6). In males, CKD fosters subfertility by leading to hypogonadism, hyperprolactinemia, erectile dysfunction (ED), and premature ejaculation (PE) (7). CKD also has direct disruption of sperm production, which can result in oligospermia or even azoospermia (2,4-8). There is also a high prevalence of sexual dysfunction in male CKD patients, which worsens with declining renal function and is associated with vascular damage, neuropathy, psychological factors, and medication use (2,7,9).

Kidney transplantation (KTx) is the definitive therapy for end-stage kidney disease (ESKD), offering patients the potential for recovery without the need for dialysis and allowing for a better quality of life (1,7,10). KTx also brings a significant effect in recalibrating the HPG axis in at least a subset of recipients thus can improve the fertility of ESKD patients (2,4,11). Hence, we report the first documented case in the literature of successful natural conception in an azoospermic male with ESKD following KTx. We present this case in accordance with the CARE reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-319/rc).

Case presentation

A 32-year-old man sought evaluation for a 4-year inability to conceive, coupled with diminished sexual drive and mild erectile difficulties. His 28-year-old spouse showed no reproductive health concerns and neither partner had a history of previous pregnancies or offspring from prior relationships. The medical history included stage 3 CKD stemming from chronic glomerulonephritis and hypertension, which progressed to ESKD without requiring dialysis, managed only with beta-blockers and calcium channel blocker. Physical examination revealed unremarkable findings, including a normal body mass index and a fully mature male urogenital appearance (Tanner stage 5). Scrotal examination revealed bilaterally small testes with palpable vas deferens on both sides and no clinical evidence of varicoceles. Initial tests revealed high serum urea (115 mg/dL), creatinine (6.2 mg/dL), and notable proteinuria, with an estimated glomerular filtration rate (eGFR) of 11.28 mL/min/1.73 m². Endocrine assessments indicated hypergonadotropic hypogonadism, marked by raised follicle-stimulating hormone (FSH) at 35.25 mIU/mL and luteinizing hormone (LH) at 17.09 mIU/mL, though morning total testosterone remained within normal range (5.09 ng/mL; see Table 1). Two semen evaluations confirmed azoospermia with reduced ejaculate volumes with no prior semen evaluation on record. Scrotal and transrectal ultrasound identified bilaterally small testes without varicocele or evidence of obstruction, such as dilated seminal vesicles or ejaculatory ducts. Genetic analysis confirmed a normal 46,XY karyotype with no Y-chromosome microdeletions.

Following the diagnosis of ESKD, and after consultation with a nephrologist, the patient was offered the options of KTx, peritoneal dialysis, or waiting until indications for regular dialysis emerged. Given the concomitant diagnosis of non-obstructive azoospermia (NOA), two fertility management strategies were considered: microdissection testicular sperm extraction (mTESE) followed by intracytoplasmic sperm injection (ICSI), or KTx with subsequent reassessment of fertility potential. After careful consideration, the patient prioritized undergoing KTx from a living unrelated donor, which led to normalization of renal function (creatinine 100 µmol/L, urea 4.48 mmol/L). At 3 months post-KTx, hormonal recovery was partial, with marked reductions in FSH and LH levels, although FSH remained mildly elevated (Table 1).

He was maintained on immunosuppressive therapy including tacrolimus, mycophenolate, and methylprednisolone with no episodes of fever or infection reported during the 3 months following KTx. Semen analysis at that time revealed restored spermatogenesis with an ejaculate volume of 2.1 mL, sperm concentration of 11 million/mL, motility of 47%, and 0% normal morphology. Additionally, the patient’s libido had normalized; however, testicular size, which was bilaterally small prior to KTx, showed no significant change post-KTx (Figure 1). Despite severely abnormal semen parameters, the couple achieved spontaneous conception without assisted reproductive technologies (ARTs) by four months post surgery. However, the pregnancy ended in miscarriage at approximately 7 weeks of gestation. The couple is currently trying to conceive naturally again while also preserving sperm for potential future ART cycles.

Figure 1 Timeline of ESKD progression in an azoospermic patient, followed by kidney transplantation and future fertility management plans. CKD, chronic kidney disease; ESKD, end-stage kidney disease; HPG, hypothalamic-pituitary-gonadal.

All procedures performed in this study were in accordance with the ethical standards of the University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam research committee, and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Infertility is defined as the inability of couples to conceive after one year of regular, unprotected intercourse. Globally, it affects around 10% of couples, with male factors contributing to nearly half of all cases (4,12). Among the established causes of male infertility—such as hormonal imbalances, varicocele, and genetic abnormalities—systemic conditions, including renal failure, are also recognized as contributing factors (8,13). CKD and its progression to ESKD compromise male reproductive health, causing endocrine imbalances, diminished sperm production. Low testosterone levels are prevalent among these patients, with ED exacerbating the physical toll of hormonal deficits (2,6). A study by Fu et al. found that elevated albumin-to-creatinine ratios (ACRs) correlated with poorer International Index of Erectile Function-5 (IIEF-5) scores, while reduced eGFR was tied to PE, underscoring the decline in sexual health with worsening kidney function (2). Dialysis patients commonly show defective sperm formation, marked by low sperm counts, poor quality, and reduced free testosterone due to impaired Leydig cell activity (7,11). CKD alters the HPG axis by impairing gonadotropin releasing hormone (GnRH) pulsatility and reducing testosterone levels, leading to disinhibited and persistently elevated LH and FSH secretion. Dysregulation of GnRH secretion—mediated by factors such as malnutrition, chronic stress, and systemic illness—further contributes to the hypogonadal state frequently observed in ESKD (7). Uremia and high prolactin levels further destabilize endocrine function, worsening ED and hypogonadism (2,14). This hormonal imbalance diminishes Sertoli cell stimulation and severely compromises spermatogenesis (3,7). In this particular case, only FSH was elevated, possibly reflecting the recent diagnosis of ESKD and the absence of an indication for regular dialysis. We suggest that with longer disease duration, abnormalities in testosterone, LH, and prolactin levels might also develop. Retrograde ejaculation was unlikely, as decreased ejaculate volume is a common finding in men with ESKD and normalized after KTx in this case (4).

For our NOA patient, we evaluated two approaches: prompt mTESE with ICSI or KTx with subsequent fertility reassessment. While mTESE may allow early sperm collection, it poses surgical risks and possible failure, alongside ART-related concerns for the female partner (15,16). KTx, conversely, promised broader health gains and hormonal stabilization, despite its own surgical demands and need for ongoing immunosuppression (7,11). Considering the couple’s age and the patient’s status, we opted for KTx first after shared decision-making. KTx lowers morbidity and mortality, enhances quality of life, and helps restore sexual function and fertility in the majority of patients with ESKD (7,11). A meta analysis by Navaneethan et al., covering 50 studies, noted ED in 75% of CKD patients, dropping to 59% after KTx, suggesting enhanced kidney function may aid sexual performance, although results depend on underlying factors (14). KTx restores renal function and eliminates uremic toxins, facilitating the recovery of the HPG axis. This results in normalized GnRH pulsatility, reduced gonadotropin levels, and improved spermatogenesis (1,7,11). In this patient, KTx led to decreased FSH levels, along with improvements in sex drive,erectile function, and spermatogenesis alongside the restoration of normal renal function. Despite a post-KTx decline in testosterone, levels remained within the normal range, with the most significant hormonal improvement observed in gonadotropin levels.

While many patients see better sperm metrics post-KTx, some still face oligoasthenoteratozoospermia. Therefore, ART remains a feasible option for post-KTx male infertility, although outcomes can be variable (4). A report by Takamoto et al. outlined two KTx-related infertility cases: one with oligoasthenozoospermia unable to conceive, and another succeeding via ICSI and mTESE due to anejaculation (9). Kaiyal et al. reported a 29-year-old male with NOA and ESKD secondary to focal segmental glomerulosclerosis. Following hemodialysis and KTx, semen analysis revealed cryptozoospermia, suggesting partial recovery of spermatogenesis (8). Similarly, our case highlights the potential for KTx to reverse CKD-associated infertility. The miscarriage at 7 weeks may stem from lingering sperm defects, indicative of incomplete spermatogenic recovery early post-KTx.

Although ending in miscarriage, this case highlights the potential for fertility restoration post-KTx, alongside challenges potentially related to sperm quality or immunosuppression (7,17). Although these agents enhance graft survival, their effects on male reproduction raise ongoing questions (4,10,17). Research on immunosuppressive drugs’ impact is more extensive for women, where some drugs are halted due to risks of genetic or developmental harm. For men, such effects are less studied, possibly because sperm mainly transfers genetic material, lacking the direct embryonic interaction seen in maternal physiology (7,10). Thus, issues like fetal drug exposure or breastfeeding concerns have centered on mothers (3,7,11). Immunosuppressive agents have varying implications for male fertility and conception. Data on stopping corticosteroids for men planning conception is limited, but they are generally continued (11,17). Calcineurin inhibitors, such as cyclosporine and tacrolimus, may lower sperm counts and motility dose-dependently, though cyclosporine rarely requires cessation and sperm banking is seldom advised but feasible. Conversely, mammalian target of rapamycin (mTOR) inhibitors like sirolimus and everolimus can disrupt the HPG axis, potentially impacting testicular functions. Sirolimus and mycophenolate mofetil carry potential teratogenic or mutagenic risks (7,10,11,18,19). In this patient, the 0% normal sperm morphology could be due to various factors, including the use of immunosuppressive drugs. Currently, there is no strong evidence linking the drugs used by this patient—tacrolimus, mycophenolate, or methylprednisolone—to teratospermia (10). However, Berkkanoglu et al. reported teratospermia in 3 out of 5 male recipients undergoing ICSI, all of whom were receiving mycophenolate therapy (20). Meanwhile, the study by Xu et al. on 212 male renal allograft recipients found that a cyclosporine A dose >2 mg/kg/day can significantly reduce sperm motility and normal sperm morphology (21). Current evidence does not clearly demonstrate a link between paternal immunosuppression after KTx and birth defects; but patients should consult healthcare providers when planning conception (7,10,11). In this case, KTx may have contributed to the restoration of fertility, potentially allowing the use of ejaculated sperm for ART in the future without the need for surgical sperm retrieval. If spontaneous pregnancy fails or results in miscarriage, ART combined with preimplantation genetic testing (PGT) could be considered to assess embryo quality and improve reproductive outcomes.

Post-KTx male fertility reflects both recovery from uremic suppression and possible drawbacks from immunosuppressive agents on hormones and spermatogenesis (4,10,17-19). To our knowledge, this marks the first documented case of an azoospermic ESKD male regaining significant sperm function and achieving natural conception after KTx. This case illustrates the capacity for restored sexual drive, erectile function, and fertility in azoospermic ESKD men post-KTx, advocating for customized infertility strategies that view KTx as a feasible path to hormonal and sperm recovery. Further study of paternal immunosuppressive effects and tailored reproductive plans is needed.

Conclusions

This case illustrates that ESKD, which causes serious health complications, may also lead to infertility or azoospermia, while KTx has the potential to reverse these effects—even in previously azoospermic men. Significant improvement in sexual health and sperm production post-KTx can facilitate natural conception. Although patient’s early pregnancy loss may relate to persistent sperm imperfections or immunosuppressive drugs, the fertility outcome is promising. This case emphasizes the need for personalized reproductive evaluations in azoospermic men with CKD or ESKD, particularly those of childbearing age. Comprehensive studies are crucial to elucidate treatment strategies and the reproductive impacts of immunosuppressive medications on paternal fertility and offspring health. Additionally, more reports on NOA patients with systemic diseases such as ESKD are needed to evaluate the role of definitive treatments in promoting potential fertility recovery.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-319/rc

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-319/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-319/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam research committee, and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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