1 Departments of Urology and Renal Transplantation, Yokohama City University Medical Center, Yokohama, Japan
2 Department of Urology, Reproduction Center, Yokohama City University Medical Center, Yokohama, Japan
3 Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan
4 Department of Urology, Yokohama City University Medical Center, Yokohama, Japan
Renal transplantation is a useful option for allowing female renal failure patients of childbearing age to achieve pregnancy. However, there have been a few reports on the effects of renal transplantation on infertility treatment in male renal failure patients. We herein report two cases in which male patients underwent infertility treatment after renal transplantation.
Case 1: A 51-year-old Asian (Japanese) man underwent transplantation (the donor was his wife) for renal failure due to Autosomal Dominant Polycystic Kidney Disease (ADPKD). At two years after transplantation, he visited the reproduction center in our institute due to infertility. A semen analysis revealed oligoasthenozoospermia. He ultimately failed to achieve pregnancy and gave up on infertility treatment.
Case 2: A 47-year-old Asian (Japanese) man underwent renal transplantation (the donor was his sister) due to renal failure caused by diabetes mellitus. At three years after renal transplantation, he visited the reproduction center in our institute for infertility. Due to ejaculation disability and the absence of sperm in the patient’s urine after masturbation, he was diagnosed with anejaculation. Thus, testicular sperm extraction (TESE) was performed. Twenty-three motile spermatozoa were successfully retrieved by microdissection TESE (micro-TESE). ICSI was subsequently performed and a good embryo was transferred. His wife achieved pregnancy and is expected to deliver this October.
We report two cases of male infertility treatment after renal transplantation.
Keywords: Male infertility, azoospermia, oligospermia, Renal transplantation, Spermatozoa, Kidney disease.
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* Address correspondence to this author at the Departments of Urology and Renal Transplantation, Yokohama City University Medical Center, Yokohama, Japan; Tel: +81-45-786-5775; E-mail: firstname.lastname@example.org
Renal transplantation is a useful option for female renal failure patients of childbearing age who wish to achieve pregnancy. Previous studies have confirmed that the fertility of some female renal failure patients was improved by renal transplantation [1Shah S, Verma P. Overview of pregnancy in renal transplant patients. Int J Nephrol 2016; 2016: 4539342.[http://dx.doi.org/10.1155/2016/4539342] [PMID: 28042483] -3Kusaka M, Kubota Y, Sasaki H, et al. Combined predictive value of the expanded donor criteria for long-term graft survival of kidneys from donors after cardiac death: A single-center experience over three decades. Int J Urol 2016; 23(4): 319-24.[http://dx.doi.org/10.1111/iju.13045] [PMID: 26790549] ]. However, there are a few reports on the effects of renal transplantation on male infertility. We herein report two cases in which male infertility treatment was performed after renal transplantation.
2. CASE PRESENTATION
2.1. Case 1
The patient was a 53-year-old Asian (Japanese) man who had received hemodialysis due to autosomal dominant poly-cystic kidney disease (ADPKD) for 12 years (Table 1). He underwent renal transplantation (the donor was his wife). At that time, neither the patient nor his wife intended to have children. Immunosuppressive treatment was initiated with Tacrolimus (Tac), Mycophenolate Mofetil (MMF), Methyl Prednisone (MP), and Basiliximab (Basi). He experienced no graft rejection and favorable control with Tac (1.5 mg/day), MMF (1.5 g/day), and MP (2 mg/day). At two years after renal transplantation, the patient indicated that he and his wife wished to have children and the patient visited the reproduction center in our institute with the chief complaint of infertility. At this time, his wife was 40 years of age.
Table 1 Patient characteristics and the clinical course.
A semen analysis revealed that the patient’s sperm con-centration was 3.69 × 106/mL and the motile sperm count was 6.67%. According to semen analysis, zoospermia was observed, therefore TESE was not performed. The bilateral testicular volume was 18 ml and no varicocele was seen. Hormone analysis revealed the following findings: prolactine, 9.7 ng/mL; testosterone, 5.03 ng/mL; LH, 4.8 IU/mL; and FSH, 8.4 IU/mL. Due to the low motile sperm count, IVF, ICSI and subsequent embryo transfer were performed. However, pregnancy was not achieved.
2.2. Case 2
The patient was a 50-year-old Asian (Japanese) man who had received hemodialysis due to diabetes mellitus for three years (Table 1). He underwent renal transplantation (the donor was his sister). Immunosuppressive therapy was initiated with Tac, MMF, MP, and Basi. He experienced no graft rejection and favorable control with Tac (4 mg/day), MMF: (1.0 g/day), and MP 5 (mg/day).
At three years after renal transplantation, he visited the reproduction center in our institute due to infertility. He had two children with his former wife before renal failure. At that time, he was fertile and the two children were conceived naturally. He had no varicocele and seminal tract obstruction. A laboratory examination revealed the following findings: pro-lactin, 20.9 ng/mL; testosterone, 5.96 ng/mL; LH, 9.1 mIU/mL; FSH, 6.8 mIU/mL. He had an ejaculatory disorder during masturbation, despite the presence of orgasm. Retrograde ejaculation was suspected; however, no sperm was found in the patient’s urine after masturbation. Thus, with a diagnosis of anejaculation due to diabetic neuropathy, 23 motile sperma-tozoa were successfully retrieved by micro-TESE.ICSI and embryo transfer were subsequently performed. Implantation and pregnancy were successfully achieved. His wife is expected to deliver this October.
3. RESULTS & DISCUSSION
One in 6 couples complains of infertility. Approximately half of such cases involve male infertility [4Chiba K, Fujisawa M. Clinical outcomes of varicocele repair in infertile men: A review. World J Mens Health 2016; 34(2): 101-9.[http://dx.doi.org/10.5534/wjmh.2016.34.2.101] [PMID: 27574593] ]. Infertility among female patients with end-stage renal disease has been exten-sively investigated. The male reproductive function in such patients is less well-characterized. Recently, some cases have been reported that showed that the genesis of the male sexual function is multifactorial [5Eckersten D, Giwercman A, Christensson A. Male patients with terminal renal failure exhibit low serum levels of antimüllerian hormone. Asian J Androl 2015; 17(1): 149-53.[http://dx.doi.org/10.4103/1008-682X.135124] [PMID: 25130586] ].
In renal failure patients, various factors result in infertility, including endocrinological abnormalities (e.g., hyperprolacti-nemia), decreased spermatogenesis through the Sertoli cells, ejaculatory disorder and erectile dysfunction, autonomic neu-ron dysfunction, iatrogenic infertility related to hemodialysis or immunosuppression, impeded blood flow due to arterioscl-erosis, and primary disease. The most commonly accepted hypothesized mechanism of infertility in renal transplantation patients is that hypergonadotropic hypogonadism occurs due to the disturbance of the hypothalamic-pituitary-gonadal axis, resulting in the suppression of spermatogenesis [6Koyun M, Baysal YE, Usta MF, Akman S, Güven AG. Evaluation of reproductive functions in male adolescents following renal transplan-tation. Pediatr Transplant 2009; 13(6): 697-700.[http://dx.doi.org/10.1111/j.1399-3046.2008.01052.x] [PMID: 189920 46] ]. After renal transplantation, the improvement of the endocrine environment results in improved fertility [7Holdsworth SR, de Kretser DM, Atkins RC. A comparison of hemodialysis and transplantation in reversing the uremic disturbance of male reproductive function. Clin Nephrol 1978; 10(4): 146-50.[PMID: 363318] ].
Generally, immunosuppressive agents do not induce sper-matogenesis or teratogenicity. On the contrary, some reports have shown that cyclosporine A has a negative impact on spermatogenesis and oogenesis [8Seethalakshmi L, Flores C, Diamond DA, Menon M. Reversal of the toxic effects of cyclosporine on male reproduction and kidney function of rats by simultaneous administration of hCG + FSH. J Urol 1990; 144(6): 1489-92.[http://dx.doi.org/10.1016/S0022-5347(17)39783-5] [PMID: 2122012] ]. Eid et al. reported that phthalic acid from the dialysis circuit reduced sperm motility in patients undergoing long-term dialysis [9Eid MM, Abdel-Hamid IA, Sobh MA, el-Saied MA. Assessment of sperm motion characteristics in infertile renal transplant recipients using computerized analysis. Int J Androl 1996; 19(6): 338-44.[http://dx.doi.org/10.1111/j.1365-2605.1996.tb00524.x] [PMID: 9051 419] ]. These findings suggest that male infertility has a multifactorial etiology; thus, it is difficult to detect specific factors causing male infertility.
In case 1, we investigated ADPDK-induced infertility. ADPKD is one of the most common monogenic human disorders and causes renal failure in a significant number of patients who require dialysis or renal transplantation. ADPKD is an inborn disease in which cysts arise in the bilateral kidneys and various organs, suppressing the renal function. Although ADPKD does not reduce infertility in comparison to the general population, male infertility has been reported to occur due to seminal vesicle cysts and azoospermia [10Cai HC, Shang XJ, Huang YF. [Related reproductive issues on male autosomal dominant polycystic kidney disease]. Zhonghua Nan Ke Xue 2015; 21(11): 1020-5. [Related reproductive issues on male autosomal dominant polycystic kidney disease].[PMID: 26738331] ].
Diabetes mellitus also affects infertility. Majzoub et al. showed that more than half of diabetes mellitus patients showed ejaculation disability [11Majzoub A, Arafa M, Al-Said S, et al. Premature ejaculation in type II diabetes mellitus patients: association with glycemic control. Transl Androl Urol 2016; 5(2): 248-54.[http://dx.doi.org/10.21037/tau.2016.03.11] [PMID: 27141454] ]. Based on these findings, it is difficult to detect the causes of infertility before renal transplantation. A hormone analysis or semen examination might help in the pre-transplantation diagnosis of male patients with infertility.
Age also affects fertility in renal male transplantation patients. Generally, the quality of sperm gradually decreases after 35 years of age [12Kidd SA, Eskenazi B, Wyrobek AJ. Effects of male age on semen quality and fertility: a review of the literature. Fertil Steril 2001; 75(2): 237-48.[http://dx.doi.org/10.1016/S0015-0282(00)01679-4] [PMID: 11172 821] ]. However, it is more difficult to set a cut-off age for male infertility than it is for female infertility.
We experienced and treated two cases of male infertility after renal transplantation. In one case, assisted pregnancy was successfully achieved.
We reported two cases of male infertility treatment after renal transplantation.
LIST OF ABBREVIATIONS
= Autosomal Dominant Polycystic Kidney Disease
= Testicular Sperm Extraction
= Mycophenolate Mofetil
= Methyl Prednisone
ETHICS APPROVAL AND CONSENT TO PARTI-CIPATE
Ethics approval and consent to participate & consent for publication were obtained.
The present study was approved by the IRB of Yokohama City University Medical Center and written informed consent was obtained from the patients. The Editor-in-Chief of this journal has a copy of the written consent available for review.
HUMAN AND ANIMAL RIGHTS
No animals/humans were used for studies that are the basis of this research.
CONSENT FOR PUBLICATION
Written informed consent was obtained from the patients for the publication of this case report and any accompanying images.
CONFLICT OF INTEREST
The authors declare no conflict of interest, financial or otherwise.
Kimitou Kobayashi and Mizuki Yamamoto supported this study.
AVAILABILITY OF DATA AND MATERIAL
Due to ethical restrictions, the raw data underlying this paper are available upon request to the corresponding author.
The present study was supported by grants from KAKENHI (16K20152), the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the 2016–2017 Research Development Fund (Nos. WJ2810) of Yokohama City University.
DT, TK, TT, TM, YH, JT SK and ST conceived and designed the experiments. DT, TK, TT, KS, YH, YM and HU analyzed the data. ST, TT, KU, KS, YH, TM, DT, YH, JT, YM, MY, YI, YY, and HU performed the experiments. KK, YY, YM, JT and HU critically revised the manuscript for important intellectual content. DT, TK and TT wrote the paper.
Okumi M, Unagami K, Tachibana H, Hirai T, Ishida H, Tanabe K. Association between body mass index and outcomes in Japanese living kidney transplant recipients: The role of sex differences. Int J Urol 2016; 23(9): 776-84.[http://dx.doi.org/10.1111/iju.13135] [PMID: 27282330]
Kusaka M, Kubota Y, Sasaki H, et al. Combined predictive value of the expanded donor criteria for long-term graft survival of kidneys from donors after cardiac death: A single-center experience over three decades. Int J Urol 2016; 23(4): 319-24.[http://dx.doi.org/10.1111/iju.13045] [PMID: 26790549]
Holdsworth SR, de Kretser DM, Atkins RC. A comparison of hemodialysis and transplantation in reversing the uremic disturbance of male reproductive function. Clin Nephrol 1978; 10(4): 146-50.[PMID: 363318]
Seethalakshmi L, Flores C, Diamond DA, Menon M. Reversal of the toxic effects of cyclosporine on male reproduction and kidney function of rats by simultaneous administration of hCG + FSH. J Urol 1990; 144(6): 1489-92.[http://dx.doi.org/10.1016/S0022-5347(17)39783-5] [PMID: 2122012]
Cai HC, Shang XJ, Huang YF. [Related reproductive issues on male autosomal dominant polycystic kidney disease]. Zhonghua Nan Ke Xue 2015; 21(11): 1020-5. [Related reproductive issues on male autosomal dominant polycystic kidney disease].[PMID: 26738331]