TESA, which was developed in 1992, is a method for retrieving sperm for use in assisted reproductive technology [3]. The procedure is also used to perform biopsy of the testis. Compared to TESE, TESA is a simpler procedure with minimal physiological consequences [4]. The majority of patients in the control group were obstructive patients. While azoospermic patients who had smaller testicular volume (< 8 mL), especially in the setting of testicular hypofunction, TESE or micro-TESE would be more appropriate in these patients.
It has been reported that intra-testicular hematoma formation occurs in 29% of diagnostic testicular biopsies [5]. However, scrotal hemorrhage was a relatively rare clinical event after TESA. In the current study of 504 TESA procedures, the incidence was only 0.8%. The difference in rates may be due to the increased use of sonographic examination. Most patients do not feel uncomfortable after TESA, and routine sonographic examination is not performed, and thus small areas of hemorrhage maybe overlooked.
At our institution, during the period from 2013 to 2015, 76 men successfully ejaculated by masturbation more than 2 times, but they were not able to ejaculation on the day of oocyte retrieval. Patients on intracavernosal injection treatment had high withdrawal rates. The most common reason for withdrawal was poor response to the therapy, followed by the inconvenience of use [6]. So they did not receive such therapy in our centre. These men passed through a procedure of relaxation, given pornographic material, mood adjusting and PDE5i drug taking, selected TESA operation finally to retrieve sperm. Although the proportion of these men who developed a scrotal hemorrhage was only 2.6%, no scrotal hemorrhage occured after same operation in the other 428 patients who did not receive a PDE5i. The results suggest that the scrotal hemorrhage in these 4 patients was related to the use of a PDE5i.
PDE5i, such as sildenafil (Viagra), vardenafil (Levitra) and tadalafil (Cialis), are used to treat erectile dysfunction. PDE5i increases nitrous oxide (NO) and cyclic guanosine monophosphate (cGMP) in the smooth muscles of the corpus cavernosum. For a PDE5i to be effective, sufficient sexual stimulation is essential [7]. The men who received a PDE5i still could not relax enough to achieve sexual arousal and could not successfully ejaculate. PDE5i are generally safe and well tolerated [8], have not been reported in association with scrotal hemorrhage events. As men were not able to ask to stop PDE5i before any surgical procedure, the rationale for excess bleeding in men taking PDE5i may not exist. Although our results showed a correlation between taking a PDE5i and scrotal hemorrhage, a cause-effect relationship could not be determined from the study design. However, the mechanism by which a PDE5i increases the risk of a scrotal hemorrhage may be as follows. First, a PDE5i results in vasodilation, and redistribution of arterial blood flow that is associated with rupture of vessels. Second, the NO and cGMP pathway might be responsible for inhibition of platelet aggregation and activation. Finally, PDE5i are considered as an antithrombotic agent [9].
The limitations of this study include its retrospective design. A prospective study should be done to validate our results. Although a large number of patients participated in this study, it appears as there were only 4 events (hematoma) in the 504 patients, which may be not enough to draw the conclusion and the results maybe only anecdotal. As ultrasound was only performed after the physician suspected a hematoma on physical exam post procedure. This may introduce significant bias and lack of certainty if there actually were many other patients that did not develop hematomas that were not detected by the clinician performing a 3 days post procedure exam. So it would be better to perform ultrasound exam at 3 days after TESA.
Although there were no sufficient evidences which could support that scrotal hemorrhage after TESA was caused by the administration of a PDE5i. Given the potential risk of scrotal hemorrhage after the ingestion of a PDE5i, it should be cautious to prescribe this medicine when the patient is likely to perform TESA. Patients were on anti-coagulants, anti-platelets, taking NSAIDs and ice scrotum may be beneficial after TESA. Although it is difficult to predict ahead who have difficulty producing a semen sample of the day of assisted reproductive technique, as all patients in the drug group had been able to produce ejaculated sperm twice prior to the procedure date. We should gain information by detailed inquiry. It would be better to prepare frozen sperm before the day of the retrieval once patient were categorized as masturbation difficulty males.