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Introduction The retrograde ejaculation could be a postoperative complication in the prostate hyperplasia surgery and a cause of male infertility in couples. We hereby report such a case which was managed with positive outcome. Case report The paper presents the case of a couple diagnosed and successfully treated for primary male infertility. The 61-year-old male partner had ejaculatory dysfunction with complete retrograde ejaculation, in urine, as a result of a transurethral resection of the prostate (TURP). The recovery of the male reproductive cells from urine and the use of assisted reproductive techniques, through the intracytoplasmic injection of sperm cells into the oocyte, have resulted in a healthy child. Conclusions The particularities of this case lie in the recognition of the importance of the urological and reproductive aspects occurred as postoperative complications due to the TURP. The detailing of the postoperative risks and the adequate substantiation of surgical protocol for benign prostate hyperplasia need to take into account the reproductive wishes and the future planning of a possible pregnancy for the couple.
The retrograde ejaculation represents the most common form of ejaculatory dysfunction,1 through which the seminal material released in the posterior urethra is eliminated in the urinary bladder.2 It can be complete or partial, and can be the result of spinal cord injury, diabetes neuropathy, or surgical post interventions for transurethral prostatectomy (TURP) and incisions of the neck of the transurethral bladder, representing a relatively rare cause (0.3-2%) of masculine infertility.2,3
Normally, urine is a toxic medium for sperm, due to a low pH and high osmolality,1 therefore, several non-invasive techniques of alkalizing have been described and suggested by some authors.4 The sperm cells were recovered from urine, following neutralization of the urinary pH. After an alkaline treatment, the bladder was voided and the sample was prepared and centrifuged, allowing to obtain viable reproductive cells used for a pregnancy in the case of such patients.
Using assisted reproduction techniques, like in vitro fertilization (IVF) and intracytoplasmic injection (ICSI) of sperm cells into the oocyte, in cases of severe masculine infertility, is an option that allows fertilization even in the case of patients with retrograde ejaculation and decreased, suboptimal sperm concentration and motility.5
The following paper presents the first case reported in Romania of a healthy child conceived with the help of assisted reproduction techniques using sperm cells from the urine of a man with retrograde ejaculation.
Case report
Anamnesis: An infertile couple, with two years of pregnancy attempt, was admitted for IVF procedure: a 39-year-old female partner, and a 61-year-old male partner. The woman was nulliparous, had autoimmune thyroiditis with euthyroid function, without any other pathologic antecedents.The male had two healthy children, one aged 32 and the other 36, from a previous marriage. Three years ago, the male partner had been diagnosed with benign prostate hyperplasia for which a radical prostatectomy was performed, using radical TURP. For approximately one year to date, the patient reported the lack of semen ejaculate after sexual intercourse.
Ethical approval: The couple was evaluated, and the treatment was performed at the Gynera Fertility Clinic, Bucharest. According to the confidentiality and ethical norms, written informed consent was obtained from the patients, and the Institutional Review Board approval was acquired from the Gynera’s Ethical Committee. The authors obtained agreement for publication any accompanying images.
Clinical examination: The female gynecologic examination detected a normal genital aspect, without any pathologies. The male urological examination resulted in a normal aspect of the testicles and epididymis, without any pain and with a normal consistency. The rectal examination confirmed the surgical absence of the prostate. Retrograde seminal ejaculation in the bladder, a complication of the TURP, was suspected as a possible male infertility cause.
Laboratory tests: Lab analyses of the female patient have shown a hormonal profile in normal ranges: the anti-Müllerian hormone (AMH) 1.92 ng/mL, prolactin 350 µUI/mL, thyroid-stimulating hormone (TSH) 2.13 µUI/mL, with an increase of thyroid antibodies (anti-TPO) 63.8 UI/mL – markers of the autoimmune thyroiditis (normal values < 34 UI/mL). In the case of the male partner, no hormonal analyses were stored in the patient’s electronic file. The sperm analysis detected aspermia (lack of seminal product in antegrade ejaculation) and post-ejaculatory urine analysis showed the presence of less than 10,000 sperm cells with 1% non-progressive motility. Seminal parameters were evaluated according to WHO 2010 criteria.6 Both partners had normal serological analyses for hepatitis B, C, syphilis, and human immunodeficiency virus (HIV).
Supplementary paraclinical investigations: Transvaginal sonography showed a normal uterus and ovaries and the presence of nine antral ovarian follicles. Abdominal and testicular male sonography showed a normal bladder, epididymis, and testicles, and a free, wide, and smooth prostatic fossa.
Treatment and management of the case: The couple was evaluated based on the options and treatment decisions. Taking into consideration the low number of sperm cells and their decreased motility, an IVF-ICSI procedure was proposed, with sperm cells obtained from either post-ejaculatory prior alkalized urine, or from surgical testicular biopsy. Controlled ovarian hyperstimulation was performed, during the IVF, and a number of eight oocytes were obtained, from which seven were mature in metaphase 2 (M2).
Urine alkalinization and preparation for ICSI technique: The partner was prepared for the surgical testicular biopsy, but also for the collection of potentially viable sperm from the post-ejaculatory urine, on the same day as the egg collection was performed. Three days prior to the oocyte collection, the male partner had followed an urine alkalizing treatment with the intent of recovery retrograde ejaculated sperm cells. He had been self-administering 1g of sodium bicarbonate (NaHCO3) four times a day, keeping account of the urinary pH daily, with the use of pH-paper strips. According to a number of authors, the optimal urinary pH value, which allows for maintenance of the viability of sperm cells, is of about 7.2-8.0, with an osmolality between 270 and 500 mOsm/kg.4 After collection and preparation of the urine sample, approximately 100,000 sperm cells with 10% progressive motility were obtained, which could be further used for the ICSI procedure. For every mature recovered oocyte, a single sperm was selected and injected into the oocyte’s cytoplasm, using an ICSI micro-injection pipette (K-MPIP-1035, 5-μm inner diameter, Cook Ireland Ltd., Ireland) – Figure 1.
Figure 1. Images of ICSI procedure on mature M2 oocyte; extruded polar body at six o’clock position indicates the oocyte maturity (600×magnification); using an ICSI pipette, a single sperm is injected through the oolemma (left image) directly into the oocyte’s cytoplasm (right image)
Source: Coricovac A., collection of the Gynera Fertility Clinic, Bucharest.Eighteen hours later, the fertilization assessment was made showing six fertilized oocytes with the presence of the two polar bodies and two pronuclei (PNs), signs of sperm-oocyte interaction (Figure 2).
Figure 2. Assessment of fertilization after 18 h post ICSI showing the aspect of the six normally fertilized oocytes; each oocyte has two extruded polar bodies and two PNs, (200×magnification)
Source: Coricovac A., collection of the Gynera Fertility Clinic, Bucharest.The development of embryos until day five was observed in sequential culture media (Sydney IVF Cleavage and Blastocyst Medium, Cook, Ireland), in low oxygen environment, in a 6% CO2, 5% O2 and 89% N2 Cook MINC incubator (Cook, Ireland), at 37°C. On day five, the assessment of the embryos was made according to Gardner’s grading system,7 and a morula and an early blastocyst (Figure 3) were transferred to the patient.
Figure 3. Aspect of day five transferred embryos (200×magnification)
A) Early Blastocyst; B) Morula.
Source: Coricovac A., collection of the Gynera Fertility Clinic, BucharestAfter ten days, the chemical pregnancy was determined and the serum hCG (human chorionic gonadotrophin) value suggested the presence of a pregnancy (158 mUI/mL). Four weeks apart from the embryo transfer, the sonography revealed one gestational sac and one embryo with rhythmic heartbeats. The patient gave birth at 38 weeks of pregnancy, to a 3,000 g, 51 cm baby boy with an Apgar score of 9.
One of the most frequent postoperative complications of TURP is retrograde ejaculation, which appears in over 70% of cases and has particular implications on the male infertility level.8 The affliction implies elimination of the seminal liquid up to the level of the posterior urethra and then subsequent regurgitation in the urinary bladder,9 followed by the sperm release in the urine and complete aspermia. To our knowledge, this is the first Romanian reported case of a healthy child obtained through assisted reproductive techniques using sperm cells recovered from post-ejaculatory urine of a man with complete aspermia following a TURP.
The acid bladder medium is toxic for the vitality of the masculine reproductive cell, affecting especially the motility.1 Therefore, many non-invasive methods have been proposed in order to reduce the destructive effect of urine on sperm cells.4 One of them, like in this case, uses alkalizing agents to neutralize urinary acidity, and then collect sperm after washing and preparing the patient's urine sample.9
Medical conditions such as diabetes, spinal cord injuries or nonspinal cord injury may lead to the appearance of the ejaculatory dysfunction.2 The management of retrograde ejaculation must take into account the etiology of the disease and will have two approaches: either the alkalinization of the urine, its preparation and use in assisted reproduction procedures, or the use of adrenergic drugs in an attempt to obtain an anterograde ejaculation.4
In this case report, both complete lack of sperm cells ejaculated anterograde and low concentration and motility for those collected from the urine, have imposed the ICSI procedure to treat a patient with severe male infertility, with the purpose of obtaining a pregnancy. The technique allows fertilization of the oocytes obtained by controlled hyperstimulation and injection of a single sperm directly into the cytoplasm of a mature oocyte, regardless of the location and origin of the sperm cells (from ejaculate, postejaculatory urine, epididymal aspirate, or those obtained by testicular biopsy).5 According to another study, ICSI was the most optimal oocyte fertilization method used on 16 couples, with seven clinical pregnancies confirmed.10
The presented case shows that for men with infertility caused by retrograde ejaculation, there are specific treatments that can allow obtaining a successful pregnancy in a couple. However, an individual evaluation and management of patients with benign prostate hyperplasia, as well as a correct risk evaluation regarding the treatment through the TURP surgical technique, should take into account the reproductive plans and patient’s wish for a future pregnancy in the couple.
1. Zhao Y, Garcia J, Jarow JP, Wallach EE. Successful management of infertility due to retrograde ejaculation using assisted reproductive technologies: a report of two cases. Arch Androl. 2004;50:391-4.
https://doi.org/10.1080/01485010490484110
2. Mehta A, Sigman M. Management of the dry ejaculate: a systematic review of aspermia and retrograde ejaculation. Fertil Steril. 2015;104:1074-81.
https://doi.org/10.1016/j.fertnstert.2015.09.024
3. Jefferys A, Siassakos D, Wardle P. The management of retrograde ejaculation: a systematic review and update. Fertil Steril. 2012;97:306-12.
https://doi.org/10.1016/j.fertnstert.2011.11.019
4. Check JH, Bollendorf AM, Press MA, Breen EM. Noninvasive techniques for improving fertility potential of retrograde ejaculates. Arch Androl. 1990;25:271-6.
https://doi.org/10.3109/01485019008987616
5. Ebner T, Shebl O, Mayer RB, Moser M, Costamoling W, Oppelt P. Healthy live birth using theophylline in a case of retrograde ejaculation and absolute asthenozoospermia. Fertil Steril. 2014;101:340-3.
https://doi.org/10.1016/j.fertnstert.2013.10.006
6. WHO laboratory manual for the examination and processing of human semen. 2010; Fith edition:F(10):286.
7. Gardner DK, Lane M, Stevens J, Schlenker T, Schoolcraft WB. Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. Fertil Steril. 2000;73:1155-8.
https://doi.org/10.1016/S0015-0282(00)00518-5
8. Liao J, Zhang X, Chen M, et al. Transurethral resection of the prostate with preservation of the bladder neck decreases postoperative retrograde ejaculation. Wideochir Inne Tech Maloinwazyjne. 2019;14:96-101.
https://doi.org/10.5114/wiitm.2018.79536
9. Glezerman M, Lunenfeld B, Potashnik G, Oelsner G, Beer R. Retrograde ejaculation: pathophysiologic aspects and report of two successfully treated cases. Fertil Steril. 1976;27:796-800.
https://doi.org/10.1016/S0015-0282(16)41955-2
10. Nikolettos N, Al-Hasani S, Baukloh V, et al. The outcome of intracytoplasmic sperm injection in patients with retrograde ejaculation. Hum Reprod. 1999;14:2293-6.
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