While postoperative pain management is an important aspect of surgical planning, approximately 5%–7% of patients who are prescribed an opioid following a minor surgical procedure will develop new persistent opioid use, which is defined as an opioid-naïve patient who later receives a narcotic prescription ≥90 days after the initial prescription.^1,2 Our study assessed the risk of new persistent opioid use in opioid-naïve men undergoing fertility procedures.

We performed a retrospective cohort study by querying the TriNetX, LLC Diamond Network database from January 2009 through March 2022, assessing electronic medical records and insurance claims from 92 health care organizations. We compared adult men ages 18–70 years old who underwent any of the following fertility surgical procedures: varicocele excision or ligation (CPT code 55530) with the exclusion of laparoscopic varicocele ligation (55550); unilateral epididymovasostomy (54900), bilateral epididymovasostomy (54901) or vasovasostomy (55400); incision biopsy of the testis (54505); unilateral or bilateral vasectomy (55250); excision of spermatocele (54840); and laparoscopic varicocele ligation (55550). The exposure of interest was opioid prescription within 2 weeks prior or 1 month after the index procedure. The outcome was new persistent opioid use (defined as receiving 1 or more opioid prescriptions 3 to 9 months after the index fertility procedure). Men were excluded if they: received an opioid prescription 2 weeks prior up to 1 year prior to the index procedure; had a diagnosis of opioid abuse (ICD-10-CM F11.1) or opioid dependence (F11.2) prior to the index procedure; or had any surgical procedure (CPT Concept ID 1003143) requiring anesthesia (1002796) between 1 and 9 months after the index procedure. Confounding variables were controlled for through propensity score matching by logistic regression for age, race, ethnicity, smoking status, mental health diagnoses, and preoperative pain diagnoses.

Figure. Risk of developing new persistent opioid use by procedure.

A total of 387,565 men were identified for our sample. The majority of men in our sample underwent vasectomy (355,879, 91.8%), spermatocele (12,553, 3.2%), or open varicocele (12,535, 3.2%). A total of 97,322 (25.1%) received an opioid prescription at time of the index fertility procedure and 290,243 (74.9%) did not receive an opioid prescription and were propensity matched on confounders. We found 4,611 (4.73%) men who were prescribed perioperative opioids developed new persistent opioid use, compared to only 2,185 (2.25%) men who were not prescribed perioperative opioids, indicating that men who received an opioid prescription for any fertility procedure were significantly more likely to develop new persistent opioid use (RR: 2.16, 95% CI: 2.05–2.27). The risk of new persistent opioid use remained elevated when procedures were assessed individually: testicular incisional biopsy (RR: 3.58, 95% CI: 1.91–2.17), open varicocelectomy (RR: 2.62, 95% CI: 2.00–3.43), vasovasostomy or epididymovasostomy (RR: 2.36, 95% CI: 1.27–4.36), laparoscopic varicocelectomy (RR: 2.07, 95% CI: 1.11–3.88) vasectomy (RR: 2.06, 95% CI: 1.95–2.17; see Figure).

We conclude that opioid-naïve men who are prescribed opioids after fertility surgeries are at a significant risk of developing new persistent opioid use. This risk is equivalent to the most common adverse events associated with these fertility procedures, including hematoma and infection. As such, it is important that urologists employ multimodal, opioid-free, postoperative analgesia strategies when appropriate and counsel their patients about this risk when prescribing perioperative opioids if unavoidable.