IVF cycles which are canceled due to an inability to obtain sperm are rare, occurring only in 0.3% of cycles (1 in 338 cycles). Here, we report the first real-world incidence of such instances based on a national cohort. Most of these couples planned to use ejaculated sperm for IVF, followed by planned use of testicular sperm. We also observed that a minority of couples attempted a subsequent cycle of IVF, with most couples utilizing the same planned sperm source.
Inability to obtain sperm is the most feared outcome for an azoospermic man undergoing planned SSR in conjunction with programmed ovulation induction, or “fresh” testicular sperm extraction (TESE). For men with azoospermia due to spermatogenic dysfunction, also known as non-obstructive azoospermia, sperm retrieval rates (SRR) remain relatively low. A recent meta-analysis showed successful retrieval occurs in only 52% of surgeries when microsurgical testicular sperm dissection is performed (Bernie, Mata, Ramasamy, & Schlegel, 2015). However, for “fresh” TESE, availability of an operating microscope may be limited as may operating room available, so a conventional non-microsurgical TESE must be carried out. For that latter procedure, successful retrieval rates are lower.
For men with obstructive azoospermia (OA), such as those who have undergone prior vasectomy, SRR should be practically 100% (Esteves et al., 2014). Even if initial percutaneous testicular or epididymal aspiration attempts are unsuccessful, a “back-up” approach employing conventional TESE will almost always be successful. Interestingly, we observed that epididymal aspirate was the planned sperm in 7% of such failed cycles. It is unclear why these couples did not undergo same-day open TESE after aspiration failed to obtain sperm. However, while nomogram predictions, reliant on testicular size and serum FSH, are highly effective at differentiating between men with ASD and idiopathic OA, they are not perfectly accurate (SCHOOR, ELHANBLY, NIEDERBERGER, & ROSS, 2002). Furthermore, men with underlying diffuse maturation arrest testicular histology may have larger testicles and relatively lower FSH, relative to other men with ASD (Weedin, Bennett, Fenig, Lamb, & Lipshultz, 2011), and may be mistakenly planned for an epididymal aspirate. Thus, scenarios in which a “fresh” TESE is planned with the assumption of a high retrieval rate due to presumed obstructive physiology, may in fact result in failure to obtain sperm due to unexpected spermatogenic dysfunction.
Our results are surprising insofar as most of the instances of inability to obtain sperm for IVF relied on ejaculated sperm, indicating varied causes including sexual dysfunction or insufficient numbers of ejaculated sperm. Delayed orgasm or anorgasmia, however transient, may ultimately be at fault. Secondary orgasm dysfunction, resulting later in life, may be due to selective serotonin reuptake inhibitors, hyperprolactinemia, chronic penile stimulation, or psychogenic/situational reasons (Jenkins & Mulhall, 2015). This result underscores the importance of a sexual history intake during the couple’s initial evaluation for infertility. Abnormal findings should prompt referral to a male reproductive medicine specialist (Penzias et al., 2018). Options for such men may include cryopreservation of ejaculated sperm ahead of time, planned electroejaculation in cases of known ejaculatory failure, penile vibratory stimulation, or even SSR. Electroejaculation has a high success rate among men with psychogenic anorgasmia, but requires sedation (Schatte, Orejuela, Lipshultz, Kim, & Lamb, 2000). One study found the risk of transient azoospermia on the day of IVF is 52% among men with a prior semen analysis with a total count less than 100,000. Thus, such men with cryptozoospermia or severe oligozoospermia are at high risk for transient azoospermia should be especially encouraged to cryopreserve sperm (Montagut et al., 2015).
Sperm cryopreservation may help avoid instances of failed IVF cycles due to an inability to obtain sperm. Cost for elective sperm cryopreservation remain high and insurance coverage in men without azoospermia is poor. Unfortunately, there is limited insurance coverage for sperm cryopreservation and out-of-pocket costs can be significant at over $1000 for processing, with further yearly fees for maintenance (Sonnenburg, Brames, Case-Eads, & Einhorn, 2015). The fertilization and pregnancy rates are similar when comparing “fresh” versus cryopreserved/thawed testicular sperm obtained from men with ASD (Ohlander, Hotaling, Kirshenbaum, Niederberger, & Eisenberg, 2014). However, even prior sperm cryopreservation may not guarantee the presence of sperm for IVF as there are rare instances of post-thaw cellular loss among men with severe oligozoospermia or cryptozoospermia (Kathrins et al., 2017). Yet, such costs of sperm cryopreservation pale in comparison the costs of a failed IVF cycle due to the unavailability of sperm.
The costs and medical risks of IVF are a concern, making it of paramount importance to avoid such instances of canceled IVF cycles. While insurance mandates for IVF coverage are expanding, in the absence of such coverage, out-of-pocket costs for IVF can exceed $20,000 (Wu, Odisho, Washington, Katz, & Smith, 2014). The risks of ovulation induction include rare instances of ovarian hyperstimulation syndrome and surgical risk, which otherwise would be avoided if IVF were forgone due to a prior knowledge of an inability to obtain sperm (Serour et al., 1998). Furthermore, one study found that only a minority of women would ultimately opt to use donor sperm after suffering a failed cycle of IVF due to an inability to surgically obtain sperm from her partner (Palermo, Neri, Schlegel, & Rosenwaks, 2014). Indeed, this attitude was confirmed in our study, as only a minority of couples attempted a further cycle of IVF after the initial failure with even fewer subsequently utilizing donor sperm.
While this is a large national cohort, one limitation includes the retrospective nature of the data. There is limited granularity regarding the underlying etiology of male factor infertility (e.g., obstructive azoospermia due to vasectomy versus spermatogenic dysfunction), which precludes further the generalizability of the results. The database does not allow for linking to previous semen analyses prior to IVF. Furthermore, the database utilized only includes data from 2014–2016 and there were only 719 total cycles in which there was failure to obtain sperm. As data from subsequent years becomes available additional conclusions may be drawn with more representative cycles. There is a need for future multi-intuitional cohorts to examine this question with more detail about the male partners history.