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Inability to obtain sperm for fresh IVF cycles: analysis and incidence of outcomes using a database from the United States

Inability to obtain sperm for fresh IVF cycles: analysis and incidence of outcomes using a... Background: Azoospermia is present in 10% of men presenting with infertility and surgical sperm retrieval rates for men with azoospermia due to spermatogenic dysfunction remain low. We investigated the incidence of failed fresh IVF cycles due to inability to obtain sperm and describe predictors for subsequent IVF. Methods: A national IVF database was used to identify fresh IVF cycles in which there was failure to obtain sperm. Patient linkage was utilized to determine outcomes of subsequent IVF. Results: 243,291 fresh IVF cycles were identified; 719 (0.3%) listed “inability to obtain sperm” as reason for embryo non-transfer. Male infertility was a factor in 537 (75%) and ejaculation was the most common anticipated sperm source (414, 57%). 713 (99.2%) cycles resulted in retrieved oocytes, but only 627 (87.2%) cryopreserved oocytes. 265 (37%) of couples underwent subsequent IVF. On multivariable analysis, lack of initial oocyte cryopreservation (OR 0.34, p = 0.01) and male infertility (OR 0.14, p = 0.01) were associated with having no subsequent cycles. Partner sperm was used in 213 (80%) second cycles and sperm retrieval method was largely conserved (181/213, 85%). Embryos were transferred in 186 (70%) second cycles. Failed embryo transfers were due to repeat inability to obtain sperm in 5 (6%) cycles. Conclusions: Failure to obtain sperm during fresh IVF is rare, but most affected couples will not pursue further cycles of IVF after their initial failed attempt. Introduction therapies is a significant stressor for couples already Azoospermia is present in 3–10% of men presenting suffering from infertility. with infertility [4, 16]. Unfortunately, surgical sperm Multiple different approaches to SSR have been pur- retrieval (SSR) rates for men with nonobstructive sued to optimize outcomes. A “fresh” SSR attempt in- azoospermia (NOA) remain low [8]. Furthermore, volves timing the man’s extraction procedure to a otherreasonsforfailure to obtain spermon the day programmed ovulation induction cycle and oocyte re- of in-vitro fertilization (IVF) include ejaculatory trieval. Failure to obtain sperm in such a scenario is par- dysfunction and transient/unexpected azoospermia. ticularly devastating for the couple. An alternative Failure to obtain sperm for assisted reproductive approach involves elective SSR with cryopreservation of sperm—if successful—and use of the thawed specimen later with in-vitro fertilization (IVF) [1]. However, there * Correspondence: ajberger@bwh.harvard.edu are technical limitations of sperm cryopreservation in Presented as a moderated poster abstract at the American Urological Association Annual Meeting May 2019, Chicago, IL this setting including rare occurrences of complete post- Division of Urology, Brigham and Women’s Hospital and Harvard Medical thaw cellular loss [6]. Thus, there is no consensus on the School, 45 Francis St ASB-II, Boston, MA 02115, USA optimal approach. Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Berger et al. Fertility Research and Practice (2020) 6:14 Page 2 of 6 While individual centers may report outcomes regard- couples) listed “inability to obtain sperm” as the reason ing canceled cycles of IVF due to inability to obtain for cycle failure, with an annual incidence of 0.3% (range sperm, there is no multi-institutional, national data on 0.2–0.4%) (Table 1). the real-world incidence. Furthermore, little is known The patient demographics for these cycles are included about the clinical follow-up for such couples regarding in Table 2. The largest group of patients were White their decision to pursue future cycles of IVF. Beyond and from the Northeast. Most had no prior pregnancies failed SSR in the setting of azoospermia, there are yet and had never pursued prior IVF cycles. Male infertility other less common reasons why sperm may not be avail- was the reason for IVF in only 537 (75%) cycles. Ejacula- able—such as failure to obtain sperm from a planned tion was the most common anticipated sperm source, ejaculated specimen—for which no incidence data exists. followed by testicular biopsy and epididymal aspirate. Herein, we sought to investigate the incidence and clin- Most (99.2%) cycles resulted in retrieved oocytes, but ical outcomes for couples whose fresh IVF cycles were oocytes were cryopreserved in only 87.2%. On univariate canceled due to an inability to obtain sperm. analyses, smoking (vs nonsmoking) as well as reporting years 2015 and 2016 (vs 2014) were associated with Materials and methods cryopreservation. On multivariable analysis, however, Exemption was obtained from Institutional Review only reporting year 2015 and location in the Northeast, Board at Brigham and Women’s Hospital for this study. Midwest, and West (vs South) were associated with oo- A retrospective analysis was performed of the Society for cyte cryopreservation (Table 3). Assisted Reproductive Technology (SART) Clinical Out- 265 (37%) of couples underwent subsequent IVF cy- come Report System database of all fresh IVF cycles for cles. On multivariable analysis, lack of cryopreservation which there was a failure to obtain sperm. SART is an of oocytes on initial cycle and an initial diagnosis of male affiliate society of the American Society of Reproductive infertility were associated with failure to undergo subse- Medicine and is a national consortium of assisted repro- quent cycles (Table 4 and Fig. 1). ductive technology centers in the U.S. Relevant data was Donor sperm was used in 52 (19%) second IVF cycles. available from 2014 to 2016. We analyzed couples’ sub- Of the couples who used partner’s sperm, the method of sequent linked cycles of IVF after their initial failed cy- sperm retrieval was largely conserved from the first IVF cles. Demographic data included region of IVF center, attempt (181/213, 85%). Embryos were transferred in ethnicity of male and female partner, obstetric history, 186 (70%) of second cycles, with a clinical pregnancy reason for IVF (multiple reasons possible), intended rate of 34% (89/265) and a live birth rate of 28% (73/ sperm source (ejaculation, epididymal aspirate, testicular 265). Failed embryo transfers during second IVF cycle extraction, electroejaculation, retrograde ejaculation). were due to repeat inability to obtain sperm (5, 6.4%), Cycles involving a gestational carrier were excluded from oocyte/embryologic reasons (52, 65.8%) and other rea- our analysis. Outcomes regarding female partner in- sons (13, 16.5%). cluded number of oocytes retrieved and the decision to cryopreserve oocytes. Discussion The statistical analyses were performed utilizing Stata IVF cycles which are canceled due to an inability to ob- 14 (College Station, TX: StataCorp LP). Chi squared tain sperm are rare, occurring only in 0.3% of cycles (1 tests and logistic regression analyses were used. A p- in 338 cycles). Here, we report the first real-world inci- value of < 0.05 was regarded as statistically significant dence of such instances based on a national cohort. and all analyses were two-tailed. Results are presented as Most of these couples planned to use ejaculated sperm odds ratios (OR). for IVF, followed by planned use of testicular sperm. We also observed that a minority of couples attempted a Results subsequent cycle of IVF, with most couples utilizing the 243,291 total fresh IVF cycles were identified from 2014 same planned sperm source. to 2016. Amongst these, 719 cycles (including 710 Table 1 Yearly incidence of sperm “no retrieval” cycles Number of cycles with failure to obtain sperm Total number of fresh IVF cycles Percentage Reporting year 2014 173 85,572 0.2% 2015 258 81,712 0.3% 2016 288 76,007 0.4% Overall 719 243,291 0.3% Berger et al. Fertility Research and Practice (2020) 6:14 Page 3 of 6 Table 2 Sperm “no retrieval” cycle demographics. Total Table 2 Sperm “no retrieval” cycle demographics. Total patients = 719 patients = 719 (Continued) Number of cycles with Number of cycles with failure to obtain sperm failure to obtain sperm Reporting year Epidiymal 50 7.0% 2014 173 24.1% Retrograde ejaculation 1 0.1% 2015 258 35.9% Electro-ejaculation 1 0.1% 2016 288 40.1% Unknown 2 0.3% Clinic region Oocytes retrieved Northeast 290 40.3% No 6 0.8% South 242 33.7% Yes 713 99.2% West 95 13.2% Oocytes frozen Midwest 92 12.8% No 92 12.8% Yes 627 87.2% Race White 216 30.0% Black 70 9.7% Inability to obtain sperm is the most feared outcome Hispanic 28 3.9% for an azoospermic man undergoing planned SSR in Asian 55 7.6% conjunction with programmed ovulation induction, or Native American 1 0.1% “fresh” testicular sperm extraction (TESE). For men with azoospermia due to spermatogenic dysfunction, also Unknown 351 48.8% known as non-obstructive azoospermia, sperm retrieval Gravidity rates (SRR) remain relatively low. A recent meta-analysis 0 447 62.2% showed successful retrieval occurs in only 52% of surger- 1 to 2 199 27.7% ies when microsurgical testicular sperm dissection is 3+ 71 9.9% performed [2]. However, for “fresh” TESE, availability of Unknown 2 0.3% an operating microscope may be limited as may operat- ing room availability, so a conventional non- Prior fresh cycles microsurgical TESE must be carried out. For that latter 0 504 70.1% procedure, successful retrieval rates are lower. 1 to 2 178 24.8% For men with obstructive azoospermia (OA), such as 3+ 37 5.1% those who have undergone prior vasectomy, SRR should Reason for infertility (more than one is possible) be practically 100% [3]. Even if initial percutaneous tes- Male infertility 537 74.7% ticular or epididymal aspiration attempts are unsuccess- ful, a “back-up” approach employing conventional TESE Endometriosis 24 3.3% will almost always be successful. Interestingly, we ob- PCOS 64 8.9% served that epididymal aspirate was the planned sperm Diminished ovarian reserve 143 19.9% in 7% of such failed cycles. It is unclear why these cou- Tubal issues 63 8.8% ples did not undergo same-day open TESE after aspir- Uterine 39 5.4% ation failed to obtain sperm. However, while nomogram Unexplained 32 4.5% predictions, reliant on testicular size and serum FSH, are highly effective at differentiating between men with Complication NOA and idiopathic OA, they are not perfectly accurate No 712 99.0% [13]. Furthermore, men with underlying diffuse matur- Yes 7 1.0% ation arrest testicular histology may have larger testicles Infection 1 0.1% and relatively lower FSH, relative to other men with Hyperstimulation 4 0.6% NOA [17], and may be mistakenly planned for an epi- Other 3 0.4% didymal aspirate. Thus, scenarios in which a “fresh” TESE is planned with the assumption of a high retrieval Sperm source rate due to presumed obstructive physiology, may in fact Ejaculation 414 57.6% result in failure to obtain sperm due to unexpected sper- Testicular 251 34.9% matogenic dysfunction. Berger et al. Fertility Research and Practice (2020) 6:14 Page 4 of 6 Fig. 1 Forest plot demonstrating multivariable analysis of predictors of undergoing subsequent cycles Our results are surprising insofar as most of the in- serotonin reuptake inhibitors, hyperprolactinemia, stances of inability to obtain sperm for IVF relied on chronic penile stimulation, or psychogenic/situational ejaculated sperm, indicating varied causes including sex- reasons [5]. This result underscores the importance of a ual dysfunction or insufficient numbers of ejaculated sexual history intake during the couple’s initial evalu- sperm. Delayed orgasm or anorgasmia, however transi- ation for infertility. Abnormal findings should prompt ent, may ultimately be at fault. Secondary orgasm dys- referral to a male reproductive medicine specialist [11]. function, resulting later in life, may be due to selective Options for such men may include cryopreservation of ejaculated sperm ahead of time, planned electroejacula- Table 3 Multivariable analysis of factors predicting tion in cases of known ejaculatory failure, penile vibra- cryopreservation of eggs tory stimulation, or even SSR. Electroejaculation has a Odds Ratio p-value [95% Conf. Interval] high success rate among men with psychogenic anorgas- mia, but requires sedation [12]. One study found the risk Female partner active smoker 1.92 0.22 0.68–5.47 of transient azoospermia on the day of IVF is 52% Female partner age 1.06 0.074 0.99–1.14 among men with a prior semen analysis with a total Male infertility diagnosis 1.11 0.809 0.48–2.59 count less than 100,000. Thus, such men with crypto- Non-white race 1.10 0.804 0.53–2.29 zoospermia or severe oligozoospermia are at high risk for transient azoospermia and should be especially en- Reporting Year couraged to cryopreserve sperm [7]. 2014 reference Sperm cryopreservation may help avoid instances of 2015 3.08 0.013 1.27–7.49 failed IVF cycles due to an inability to obtain sperm. 2016 1.69 0.284 0.65–4.41 Cost for elective sperm cryopreservation remain high and insurance coverage in men without azoospermia is Region poor. Unfortunately, there is limited insurance coverage for sperm cryopreservation and out-of-pocket costs can South reference be significant at over $1000 for processing, with further Northeast 3.32 0.004 1.47–7.48 yearly fees for maintenance [15]. The fertilization and Midwest 3.40 0.033 1.1–10.44 pregnancy rates are similar when comparing “fresh” ver- West 5.06 0.005 1.64–15.58 sus cryopreserved/thawed testicular sperm obtained Berger et al. Fertility Research and Practice (2020) 6:14 Page 5 of 6 Table 4 Multivariable analysis of predictors of undergoing subsequent cycles Odds Ratio p-value [95% Conf. Interval] Female partner active smoker 1.06 0.87 0.55 2.04 Female partner age 0.97 0.20 0.93 1.02 Male infertility diagnosis 0.14 0.01 0.28 0.84 Non-white race 0.78 0.30 0.48 1.25 Reporting Year 2014 reference 2015 0.95 0.86 0.52 1.72 2016 0.61 0.17 0.31 1.23 Region Northeast reference South 1.79 0.07 0.95 3.40 West 0.97 0.93 0.43 2.18 Southwest 1.96 0.09 0.91 4.19 No frozen oocytes on prior cycle 0.34 0.01 0.15 0.76 from men with NOA [9]. However, even prior sperm sperm. As data from subsequent years becomes available cryopreservation may not guarantee the presence of additional conclusions may be drawn with more repre- sperm for IVF as there are rare instances of post-thaw sentative cycles. A future area of potential study is com- cellular loss among men with severe oligozoospermia or paring this data from the United States with data cryptozoospermia [6]. Yet, such costs of sperm cryo- obtained within similar databases in other countries. preservation pale in comparison to the costs of a failed Furthermore, there is a need for future multi-intuitional IVF cycle due to the unavailability of sperm. cohorts to examine this question with more detail about The costs and medical risks of IVF are a concern, the male partners history. making it of paramount importance to avoid such in- stances of canceled IVF cycles. While insurance man- Conclusion dates for IVF coverage are expanding, in the absence of This study shows that IVF cycles are only rarely can- such coverage, out-of-pocket costs for IVF can exceed celed to an inability to obtain sperm. Ejaculated sperm $20,000 [18]. The risks of ovulation induction include was the most common expected source of sperm leading rare instances of ovarian hyperstimulation syndrome and to cancelation. Most affected couples will not pursue surgical risk, which otherwise would be avoided if IVF further cycles of IVF after their initial failed attempt. were forgone due to a prior knowledge of an inability to Acknowledgements obtain sperm [14]. Furthermore, one study found that None only a minority of women would ultimately opt to use Capsule donor sperm after suffering a failed cycle of IVF due to Failure to obtain sperm during fresh IVF cycles is a rare occurrence, most an inability to surgically obtain sperm from her partner often resulting due to inability to provide an ejaculated specimen. A [10]. Indeed, this attitude was confirmed in our study, as minority of affected couples pursued further cycles of IVF. only a minority of couples attempted a further cycle of Authors’ contributions IVF after the initial failure with even fewer subsequently AJB assisted with study design, performed statistical analyses and was a utilizing donor sperm. major contributor in writing the manuscript. VP assisted with study hypothesis and design and contributed to writing the manuscript. RAG While this is a large national cohort, one limitation in- assisted with study hypothesis and design and contributed to writing the cludes the retrospective nature of the data. There is lim- manuscript. AL assisted with statistical design and performed statistical ited granularity regarding the underlying etiology of analyses. MK was the study originator, major contributor to study hypothesis and design and was a major contributor in writing the manuscript. All male factor infertility (e.g., obstructive azoospermia due authors read and approved the final manuscript. to vasectomy versus spermatogenic dysfunction), which precludes further the generalizability of the results. The Funding Not applicable database does not allow for linking to previous semen analyses prior to IVF. Furthermore, the database utilized Availability of data and materials only includes data from 2014 to 2016 and there were The datasets during and/or analyzed during the current study available from only 719 total cycles in which there was failure to obtain the corresponding author on reasonable request. Berger et al. Fertility Research and Practice (2020) 6:14 Page 6 of 6 Ethics approval and consent to participate 15. Sonnenburg DW, Brames MJ, Case-Eads S, Einhorn LH. Utilization of sperm Exemption was obtained from Institutional Review Board at Brigham and banking and barriers to its use in testicular cancer patients. Support Care Women’s Hospital for this study. Cancer. 2015;23(9):2763–8. https://doi.org/10.1007/s00520-015-2641-9. 16. Thonneau P, Marchand S, Tallec A, Ferial M-L, Ducot B, Lansac J, et al. Incidence and main causes of infertility in a resident population (1 850 000) Consent for publication of three French regions (1988–1989)*. Hum Reprod. 1991;6(6):811–6. https:// Not applicable doi.org/10.1093/oxfordjournals.humrep.a137433. 17. Weedin J, Bennett R, Fenig D, Lamb D, Lipshultz L. Early versus late Competing interests maturation arrest: reproductive outcomes of testicular failure. J Urol. 2011; The authors declare that they have no competing interests 186(2):621–6. https://doi.org/10.1038/nature11130.Reduced. 18. Wu AK, Odisho AY, Washington SL, Katz PP, Smith JF. Out-of-pocket fertility Author details patient expense: data from a multicenter prospective infertility cohort. J Division of Urology, Brigham and Women’s Hospital and Harvard Medical Urol. 2014;191(2):427–32. https://doi.org/10.1016/j.juro.2013.08.083. School, 45 Francis St ASB-II, Boston, MA 02115, USA. Department of Obstetrics and Gynecology, Center for Infertility and Reproductive Surgery, Brigham and Women’s Hospital and Harvard Medical School, 75 Francis Publisher’sNote Street, Boston, MA 02115, USA. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Received: 27 February 2020 Accepted: 13 July 2020 References 1. Anger JT, Gilbert BR, Goldstein M. Cryopreservation of sperm: indications, methods and results. J Urol. 2003;170(4):1079–84. https://doi.org/10.1097/01. JU.0000084820.98430.B8. 2. Bernie AM, Mata DA, Ramasamy R, Schlegel PN. Comparison of microdissection testicular sperm extraction, conventional testicular sperm extraction, and testicular sperm aspiration for nonobstructive azoospermia: a systematic review and meta-analysis. Fertility Sterility. 2015;104(5):1099– 1103.e3. https://doi.org/10.1016/J.FERTNSTERT.2015.07.1136. 3. Esteves S, Prudencio C, Seol B, Verza S, Knoedler C, Agarwal A. Comparison of sperm retrieval and reproductive outcome in azoospermic men with testicular failure and obstructive azoospermia treated for infertility. Asian J Androl. 2014;16(4):602. https://doi.org/10.4103/1008-682x.126015. 4. Hull MG, Glazener CM, Kelly NJ, Conway DI, Foster PA, Hinton RA, et al. Population study of causes, treatment, and outcome of infertility. Br Med J (Clin Res Ed). 1985;291(6510):1693–7. https://doi.org/10.1136/bmj.291.6510. 5. Jenkins LC, Mulhall JP. Delayed orgasm and anorgasmia. Fertil Steril. 2015; 104(5):1082–8. https://doi.org/10.1016/J.FERTNSTERT.2015.09.029. 6. Kathrins M, Abhyankar N, Shoshany O, Liebermann J, Uhler M, Prins G, Niederberger C. Post-thaw recovery of rare or very low concentrations of cryopreserved human sperm. Fertil Steril. 2017;107(6):1300–4. https://doi. org/10.1016/j.fertnstert.2017.04.016. 7. Montagut M, Gatimel N, Bourdet-Loubère S, Daudin M, Bujan L, Mieusset R, et al. Sperm freezing to address the risk of azoospermia on the day of ICSI. Hum Reprod. 2015;30(11):2486–92. https://doi.org/10.1093/humrep/dev234. 8. Nicopoullos JDM, Gilling-Smith C, Almeida PA, Norman-Taylor J, Grace I, Ramsay JWA. Use of surgical sperm retrieval in azoospermic men: a meta- analysis. Fertil Steril. 2004;82(3):691–701. https://doi.org/10.1016/j.fertnstert. 2004.02.116. 9. Ohlander S, Hotaling J, Kirshenbaum E, Niederberger C, Eisenberg ML. Impact of fresh versus cryopreserved testicular sperm upon intracytoplasmic sperm injection pregnancy outcomes in men with azoospermia due to spermatogenic dysfunction: a meta-analysis. Fertil Steril. 2014;101(2):344–9. https://doi.org/10.1016/j.fertnstert.2013.10.012. 10. Palermo GD, Neri QV, Schlegel PN, Rosenwaks Z. Intracytoplasmic sperm injection (ICSI) in extreme cases of male infertility. PLoS One. 2014;9(12): e113671. https://doi.org/10.1371/journal.pone.0113671. 11. Penzias A, Bendikson K, Butts S, Coutifaris C, Falcone T, Fossum G, et al. Diagnostic evaluation of sexual dysfunction in the male partner in the setting of infertility: a committee opinion. Fertil Steril. 2018;110(5):833–7. https://doi.org/10.1016/j.fertnstert.2018.07.010. 12. Schatte EC, Orejuela FJ, Lipshultz LI, Kim ED, Lamb DJ. Treatment of infertility due to anejaculation in the male with electroejaculation and intracytoplasmic sperm injection. J Urol. 2000;163(6):1717–20. 13. SCHOOR RA, ELHANBLY S, NIEDERBERGER CS, ROSS LS. The role of testicular biopsy in the modern management of male infertility. J Urol. 2002;167(1): 197–200. https://doi.org/10.1016/S0022-5347(05)65411-0. 14. Serour GI, Aboulghar M, Mansour R, Sattar MA, Amin Y, Aboulghar H. Complications of medically assisted conception in 3,500 cycles. Fertil Steril. 1998;70(4):638–42. https://doi.org/10.1016/S0015-0282(98)00250-7. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Fertility Research and Practice Springer Journals

Inability to obtain sperm for fresh IVF cycles: analysis and incidence of outcomes using a database from the United States

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10.1186/s40738-020-00082-3
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Abstract

Background: Azoospermia is present in 10% of men presenting with infertility and surgical sperm retrieval rates for men with azoospermia due to spermatogenic dysfunction remain low. We investigated the incidence of failed fresh IVF cycles due to inability to obtain sperm and describe predictors for subsequent IVF. Methods: A national IVF database was used to identify fresh IVF cycles in which there was failure to obtain sperm. Patient linkage was utilized to determine outcomes of subsequent IVF. Results: 243,291 fresh IVF cycles were identified; 719 (0.3%) listed “inability to obtain sperm” as reason for embryo non-transfer. Male infertility was a factor in 537 (75%) and ejaculation was the most common anticipated sperm source (414, 57%). 713 (99.2%) cycles resulted in retrieved oocytes, but only 627 (87.2%) cryopreserved oocytes. 265 (37%) of couples underwent subsequent IVF. On multivariable analysis, lack of initial oocyte cryopreservation (OR 0.34, p = 0.01) and male infertility (OR 0.14, p = 0.01) were associated with having no subsequent cycles. Partner sperm was used in 213 (80%) second cycles and sperm retrieval method was largely conserved (181/213, 85%). Embryos were transferred in 186 (70%) second cycles. Failed embryo transfers were due to repeat inability to obtain sperm in 5 (6%) cycles. Conclusions: Failure to obtain sperm during fresh IVF is rare, but most affected couples will not pursue further cycles of IVF after their initial failed attempt. Introduction therapies is a significant stressor for couples already Azoospermia is present in 3–10% of men presenting suffering from infertility. with infertility [4, 16]. Unfortunately, surgical sperm Multiple different approaches to SSR have been pur- retrieval (SSR) rates for men with nonobstructive sued to optimize outcomes. A “fresh” SSR attempt in- azoospermia (NOA) remain low [8]. Furthermore, volves timing the man’s extraction procedure to a otherreasonsforfailure to obtain spermon the day programmed ovulation induction cycle and oocyte re- of in-vitro fertilization (IVF) include ejaculatory trieval. Failure to obtain sperm in such a scenario is par- dysfunction and transient/unexpected azoospermia. ticularly devastating for the couple. An alternative Failure to obtain sperm for assisted reproductive approach involves elective SSR with cryopreservation of sperm—if successful—and use of the thawed specimen later with in-vitro fertilization (IVF) [1]. However, there * Correspondence: ajberger@bwh.harvard.edu are technical limitations of sperm cryopreservation in Presented as a moderated poster abstract at the American Urological Association Annual Meeting May 2019, Chicago, IL this setting including rare occurrences of complete post- Division of Urology, Brigham and Women’s Hospital and Harvard Medical thaw cellular loss [6]. Thus, there is no consensus on the School, 45 Francis St ASB-II, Boston, MA 02115, USA optimal approach. Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Berger et al. Fertility Research and Practice (2020) 6:14 Page 2 of 6 While individual centers may report outcomes regard- couples) listed “inability to obtain sperm” as the reason ing canceled cycles of IVF due to inability to obtain for cycle failure, with an annual incidence of 0.3% (range sperm, there is no multi-institutional, national data on 0.2–0.4%) (Table 1). the real-world incidence. Furthermore, little is known The patient demographics for these cycles are included about the clinical follow-up for such couples regarding in Table 2. The largest group of patients were White their decision to pursue future cycles of IVF. Beyond and from the Northeast. Most had no prior pregnancies failed SSR in the setting of azoospermia, there are yet and had never pursued prior IVF cycles. Male infertility other less common reasons why sperm may not be avail- was the reason for IVF in only 537 (75%) cycles. Ejacula- able—such as failure to obtain sperm from a planned tion was the most common anticipated sperm source, ejaculated specimen—for which no incidence data exists. followed by testicular biopsy and epididymal aspirate. Herein, we sought to investigate the incidence and clin- Most (99.2%) cycles resulted in retrieved oocytes, but ical outcomes for couples whose fresh IVF cycles were oocytes were cryopreserved in only 87.2%. On univariate canceled due to an inability to obtain sperm. analyses, smoking (vs nonsmoking) as well as reporting years 2015 and 2016 (vs 2014) were associated with Materials and methods cryopreservation. On multivariable analysis, however, Exemption was obtained from Institutional Review only reporting year 2015 and location in the Northeast, Board at Brigham and Women’s Hospital for this study. Midwest, and West (vs South) were associated with oo- A retrospective analysis was performed of the Society for cyte cryopreservation (Table 3). Assisted Reproductive Technology (SART) Clinical Out- 265 (37%) of couples underwent subsequent IVF cy- come Report System database of all fresh IVF cycles for cles. On multivariable analysis, lack of cryopreservation which there was a failure to obtain sperm. SART is an of oocytes on initial cycle and an initial diagnosis of male affiliate society of the American Society of Reproductive infertility were associated with failure to undergo subse- Medicine and is a national consortium of assisted repro- quent cycles (Table 4 and Fig. 1). ductive technology centers in the U.S. Relevant data was Donor sperm was used in 52 (19%) second IVF cycles. available from 2014 to 2016. We analyzed couples’ sub- Of the couples who used partner’s sperm, the method of sequent linked cycles of IVF after their initial failed cy- sperm retrieval was largely conserved from the first IVF cles. Demographic data included region of IVF center, attempt (181/213, 85%). Embryos were transferred in ethnicity of male and female partner, obstetric history, 186 (70%) of second cycles, with a clinical pregnancy reason for IVF (multiple reasons possible), intended rate of 34% (89/265) and a live birth rate of 28% (73/ sperm source (ejaculation, epididymal aspirate, testicular 265). Failed embryo transfers during second IVF cycle extraction, electroejaculation, retrograde ejaculation). were due to repeat inability to obtain sperm (5, 6.4%), Cycles involving a gestational carrier were excluded from oocyte/embryologic reasons (52, 65.8%) and other rea- our analysis. Outcomes regarding female partner in- sons (13, 16.5%). cluded number of oocytes retrieved and the decision to cryopreserve oocytes. Discussion The statistical analyses were performed utilizing Stata IVF cycles which are canceled due to an inability to ob- 14 (College Station, TX: StataCorp LP). Chi squared tain sperm are rare, occurring only in 0.3% of cycles (1 tests and logistic regression analyses were used. A p- in 338 cycles). Here, we report the first real-world inci- value of < 0.05 was regarded as statistically significant dence of such instances based on a national cohort. and all analyses were two-tailed. Results are presented as Most of these couples planned to use ejaculated sperm odds ratios (OR). for IVF, followed by planned use of testicular sperm. We also observed that a minority of couples attempted a Results subsequent cycle of IVF, with most couples utilizing the 243,291 total fresh IVF cycles were identified from 2014 same planned sperm source. to 2016. Amongst these, 719 cycles (including 710 Table 1 Yearly incidence of sperm “no retrieval” cycles Number of cycles with failure to obtain sperm Total number of fresh IVF cycles Percentage Reporting year 2014 173 85,572 0.2% 2015 258 81,712 0.3% 2016 288 76,007 0.4% Overall 719 243,291 0.3% Berger et al. Fertility Research and Practice (2020) 6:14 Page 3 of 6 Table 2 Sperm “no retrieval” cycle demographics. Total Table 2 Sperm “no retrieval” cycle demographics. Total patients = 719 patients = 719 (Continued) Number of cycles with Number of cycles with failure to obtain sperm failure to obtain sperm Reporting year Epidiymal 50 7.0% 2014 173 24.1% Retrograde ejaculation 1 0.1% 2015 258 35.9% Electro-ejaculation 1 0.1% 2016 288 40.1% Unknown 2 0.3% Clinic region Oocytes retrieved Northeast 290 40.3% No 6 0.8% South 242 33.7% Yes 713 99.2% West 95 13.2% Oocytes frozen Midwest 92 12.8% No 92 12.8% Yes 627 87.2% Race White 216 30.0% Black 70 9.7% Inability to obtain sperm is the most feared outcome Hispanic 28 3.9% for an azoospermic man undergoing planned SSR in Asian 55 7.6% conjunction with programmed ovulation induction, or Native American 1 0.1% “fresh” testicular sperm extraction (TESE). For men with azoospermia due to spermatogenic dysfunction, also Unknown 351 48.8% known as non-obstructive azoospermia, sperm retrieval Gravidity rates (SRR) remain relatively low. A recent meta-analysis 0 447 62.2% showed successful retrieval occurs in only 52% of surger- 1 to 2 199 27.7% ies when microsurgical testicular sperm dissection is 3+ 71 9.9% performed [2]. However, for “fresh” TESE, availability of Unknown 2 0.3% an operating microscope may be limited as may operat- ing room availability, so a conventional non- Prior fresh cycles microsurgical TESE must be carried out. For that latter 0 504 70.1% procedure, successful retrieval rates are lower. 1 to 2 178 24.8% For men with obstructive azoospermia (OA), such as 3+ 37 5.1% those who have undergone prior vasectomy, SRR should Reason for infertility (more than one is possible) be practically 100% [3]. Even if initial percutaneous tes- Male infertility 537 74.7% ticular or epididymal aspiration attempts are unsuccess- ful, a “back-up” approach employing conventional TESE Endometriosis 24 3.3% will almost always be successful. Interestingly, we ob- PCOS 64 8.9% served that epididymal aspirate was the planned sperm Diminished ovarian reserve 143 19.9% in 7% of such failed cycles. It is unclear why these cou- Tubal issues 63 8.8% ples did not undergo same-day open TESE after aspir- Uterine 39 5.4% ation failed to obtain sperm. However, while nomogram Unexplained 32 4.5% predictions, reliant on testicular size and serum FSH, are highly effective at differentiating between men with Complication NOA and idiopathic OA, they are not perfectly accurate No 712 99.0% [13]. Furthermore, men with underlying diffuse matur- Yes 7 1.0% ation arrest testicular histology may have larger testicles Infection 1 0.1% and relatively lower FSH, relative to other men with Hyperstimulation 4 0.6% NOA [17], and may be mistakenly planned for an epi- Other 3 0.4% didymal aspirate. Thus, scenarios in which a “fresh” TESE is planned with the assumption of a high retrieval Sperm source rate due to presumed obstructive physiology, may in fact Ejaculation 414 57.6% result in failure to obtain sperm due to unexpected sper- Testicular 251 34.9% matogenic dysfunction. Berger et al. Fertility Research and Practice (2020) 6:14 Page 4 of 6 Fig. 1 Forest plot demonstrating multivariable analysis of predictors of undergoing subsequent cycles Our results are surprising insofar as most of the in- serotonin reuptake inhibitors, hyperprolactinemia, stances of inability to obtain sperm for IVF relied on chronic penile stimulation, or psychogenic/situational ejaculated sperm, indicating varied causes including sex- reasons [5]. This result underscores the importance of a ual dysfunction or insufficient numbers of ejaculated sexual history intake during the couple’s initial evalu- sperm. Delayed orgasm or anorgasmia, however transi- ation for infertility. Abnormal findings should prompt ent, may ultimately be at fault. Secondary orgasm dys- referral to a male reproductive medicine specialist [11]. function, resulting later in life, may be due to selective Options for such men may include cryopreservation of ejaculated sperm ahead of time, planned electroejacula- Table 3 Multivariable analysis of factors predicting tion in cases of known ejaculatory failure, penile vibra- cryopreservation of eggs tory stimulation, or even SSR. Electroejaculation has a Odds Ratio p-value [95% Conf. Interval] high success rate among men with psychogenic anorgas- mia, but requires sedation [12]. One study found the risk Female partner active smoker 1.92 0.22 0.68–5.47 of transient azoospermia on the day of IVF is 52% Female partner age 1.06 0.074 0.99–1.14 among men with a prior semen analysis with a total Male infertility diagnosis 1.11 0.809 0.48–2.59 count less than 100,000. Thus, such men with crypto- Non-white race 1.10 0.804 0.53–2.29 zoospermia or severe oligozoospermia are at high risk for transient azoospermia and should be especially en- Reporting Year couraged to cryopreserve sperm [7]. 2014 reference Sperm cryopreservation may help avoid instances of 2015 3.08 0.013 1.27–7.49 failed IVF cycles due to an inability to obtain sperm. 2016 1.69 0.284 0.65–4.41 Cost for elective sperm cryopreservation remain high and insurance coverage in men without azoospermia is Region poor. Unfortunately, there is limited insurance coverage for sperm cryopreservation and out-of-pocket costs can South reference be significant at over $1000 for processing, with further Northeast 3.32 0.004 1.47–7.48 yearly fees for maintenance [15]. The fertilization and Midwest 3.40 0.033 1.1–10.44 pregnancy rates are similar when comparing “fresh” ver- West 5.06 0.005 1.64–15.58 sus cryopreserved/thawed testicular sperm obtained Berger et al. Fertility Research and Practice (2020) 6:14 Page 5 of 6 Table 4 Multivariable analysis of predictors of undergoing subsequent cycles Odds Ratio p-value [95% Conf. Interval] Female partner active smoker 1.06 0.87 0.55 2.04 Female partner age 0.97 0.20 0.93 1.02 Male infertility diagnosis 0.14 0.01 0.28 0.84 Non-white race 0.78 0.30 0.48 1.25 Reporting Year 2014 reference 2015 0.95 0.86 0.52 1.72 2016 0.61 0.17 0.31 1.23 Region Northeast reference South 1.79 0.07 0.95 3.40 West 0.97 0.93 0.43 2.18 Southwest 1.96 0.09 0.91 4.19 No frozen oocytes on prior cycle 0.34 0.01 0.15 0.76 from men with NOA [9]. However, even prior sperm sperm. As data from subsequent years becomes available cryopreservation may not guarantee the presence of additional conclusions may be drawn with more repre- sperm for IVF as there are rare instances of post-thaw sentative cycles. A future area of potential study is com- cellular loss among men with severe oligozoospermia or paring this data from the United States with data cryptozoospermia [6]. Yet, such costs of sperm cryo- obtained within similar databases in other countries. preservation pale in comparison to the costs of a failed Furthermore, there is a need for future multi-intuitional IVF cycle due to the unavailability of sperm. cohorts to examine this question with more detail about The costs and medical risks of IVF are a concern, the male partners history. making it of paramount importance to avoid such in- stances of canceled IVF cycles. While insurance man- Conclusion dates for IVF coverage are expanding, in the absence of This study shows that IVF cycles are only rarely can- such coverage, out-of-pocket costs for IVF can exceed celed to an inability to obtain sperm. Ejaculated sperm $20,000 [18]. The risks of ovulation induction include was the most common expected source of sperm leading rare instances of ovarian hyperstimulation syndrome and to cancelation. Most affected couples will not pursue surgical risk, which otherwise would be avoided if IVF further cycles of IVF after their initial failed attempt. were forgone due to a prior knowledge of an inability to Acknowledgements obtain sperm [14]. Furthermore, one study found that None only a minority of women would ultimately opt to use Capsule donor sperm after suffering a failed cycle of IVF due to Failure to obtain sperm during fresh IVF cycles is a rare occurrence, most an inability to surgically obtain sperm from her partner often resulting due to inability to provide an ejaculated specimen. A [10]. Indeed, this attitude was confirmed in our study, as minority of affected couples pursued further cycles of IVF. only a minority of couples attempted a further cycle of Authors’ contributions IVF after the initial failure with even fewer subsequently AJB assisted with study design, performed statistical analyses and was a utilizing donor sperm. major contributor in writing the manuscript. VP assisted with study hypothesis and design and contributed to writing the manuscript. RAG While this is a large national cohort, one limitation in- assisted with study hypothesis and design and contributed to writing the cludes the retrospective nature of the data. There is lim- manuscript. AL assisted with statistical design and performed statistical ited granularity regarding the underlying etiology of analyses. MK was the study originator, major contributor to study hypothesis and design and was a major contributor in writing the manuscript. All male factor infertility (e.g., obstructive azoospermia due authors read and approved the final manuscript. to vasectomy versus spermatogenic dysfunction), which precludes further the generalizability of the results. The Funding Not applicable database does not allow for linking to previous semen analyses prior to IVF. Furthermore, the database utilized Availability of data and materials only includes data from 2014 to 2016 and there were The datasets during and/or analyzed during the current study available from only 719 total cycles in which there was failure to obtain the corresponding author on reasonable request. Berger et al. Fertility Research and Practice (2020) 6:14 Page 6 of 6 Ethics approval and consent to participate 15. Sonnenburg DW, Brames MJ, Case-Eads S, Einhorn LH. Utilization of sperm Exemption was obtained from Institutional Review Board at Brigham and banking and barriers to its use in testicular cancer patients. Support Care Women’s Hospital for this study. Cancer. 2015;23(9):2763–8. https://doi.org/10.1007/s00520-015-2641-9. 16. Thonneau P, Marchand S, Tallec A, Ferial M-L, Ducot B, Lansac J, et al. Incidence and main causes of infertility in a resident population (1 850 000) Consent for publication of three French regions (1988–1989)*. Hum Reprod. 1991;6(6):811–6. https:// Not applicable doi.org/10.1093/oxfordjournals.humrep.a137433. 17. Weedin J, Bennett R, Fenig D, Lamb D, Lipshultz L. Early versus late Competing interests maturation arrest: reproductive outcomes of testicular failure. J Urol. 2011; The authors declare that they have no competing interests 186(2):621–6. https://doi.org/10.1038/nature11130.Reduced. 18. Wu AK, Odisho AY, Washington SL, Katz PP, Smith JF. Out-of-pocket fertility Author details patient expense: data from a multicenter prospective infertility cohort. J Division of Urology, Brigham and Women’s Hospital and Harvard Medical Urol. 2014;191(2):427–32. https://doi.org/10.1016/j.juro.2013.08.083. School, 45 Francis St ASB-II, Boston, MA 02115, USA. Department of Obstetrics and Gynecology, Center for Infertility and Reproductive Surgery, Brigham and Women’s Hospital and Harvard Medical School, 75 Francis Publisher’sNote Street, Boston, MA 02115, USA. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Received: 27 February 2020 Accepted: 13 July 2020 References 1. Anger JT, Gilbert BR, Goldstein M. Cryopreservation of sperm: indications, methods and results. J Urol. 2003;170(4):1079–84. https://doi.org/10.1097/01. JU.0000084820.98430.B8. 2. Bernie AM, Mata DA, Ramasamy R, Schlegel PN. Comparison of microdissection testicular sperm extraction, conventional testicular sperm extraction, and testicular sperm aspiration for nonobstructive azoospermia: a systematic review and meta-analysis. Fertility Sterility. 2015;104(5):1099– 1103.e3. https://doi.org/10.1016/J.FERTNSTERT.2015.07.1136. 3. Esteves S, Prudencio C, Seol B, Verza S, Knoedler C, Agarwal A. Comparison of sperm retrieval and reproductive outcome in azoospermic men with testicular failure and obstructive azoospermia treated for infertility. Asian J Androl. 2014;16(4):602. https://doi.org/10.4103/1008-682x.126015. 4. Hull MG, Glazener CM, Kelly NJ, Conway DI, Foster PA, Hinton RA, et al. Population study of causes, treatment, and outcome of infertility. Br Med J (Clin Res Ed). 1985;291(6510):1693–7. https://doi.org/10.1136/bmj.291.6510. 5. Jenkins LC, Mulhall JP. Delayed orgasm and anorgasmia. Fertil Steril. 2015; 104(5):1082–8. https://doi.org/10.1016/J.FERTNSTERT.2015.09.029. 6. Kathrins M, Abhyankar N, Shoshany O, Liebermann J, Uhler M, Prins G, Niederberger C. Post-thaw recovery of rare or very low concentrations of cryopreserved human sperm. Fertil Steril. 2017;107(6):1300–4. https://doi. org/10.1016/j.fertnstert.2017.04.016. 7. Montagut M, Gatimel N, Bourdet-Loubère S, Daudin M, Bujan L, Mieusset R, et al. Sperm freezing to address the risk of azoospermia on the day of ICSI. Hum Reprod. 2015;30(11):2486–92. https://doi.org/10.1093/humrep/dev234. 8. Nicopoullos JDM, Gilling-Smith C, Almeida PA, Norman-Taylor J, Grace I, Ramsay JWA. Use of surgical sperm retrieval in azoospermic men: a meta- analysis. Fertil Steril. 2004;82(3):691–701. https://doi.org/10.1016/j.fertnstert. 2004.02.116. 9. Ohlander S, Hotaling J, Kirshenbaum E, Niederberger C, Eisenberg ML. Impact of fresh versus cryopreserved testicular sperm upon intracytoplasmic sperm injection pregnancy outcomes in men with azoospermia due to spermatogenic dysfunction: a meta-analysis. Fertil Steril. 2014;101(2):344–9. https://doi.org/10.1016/j.fertnstert.2013.10.012. 10. Palermo GD, Neri QV, Schlegel PN, Rosenwaks Z. Intracytoplasmic sperm injection (ICSI) in extreme cases of male infertility. PLoS One. 2014;9(12): e113671. https://doi.org/10.1371/journal.pone.0113671. 11. Penzias A, Bendikson K, Butts S, Coutifaris C, Falcone T, Fossum G, et al. Diagnostic evaluation of sexual dysfunction in the male partner in the setting of infertility: a committee opinion. Fertil Steril. 2018;110(5):833–7. https://doi.org/10.1016/j.fertnstert.2018.07.010. 12. Schatte EC, Orejuela FJ, Lipshultz LI, Kim ED, Lamb DJ. Treatment of infertility due to anejaculation in the male with electroejaculation and intracytoplasmic sperm injection. J Urol. 2000;163(6):1717–20. 13. SCHOOR RA, ELHANBLY S, NIEDERBERGER CS, ROSS LS. The role of testicular biopsy in the modern management of male infertility. J Urol. 2002;167(1): 197–200. https://doi.org/10.1016/S0022-5347(05)65411-0. 14. Serour GI, Aboulghar M, Mansour R, Sattar MA, Amin Y, Aboulghar H. Complications of medically assisted conception in 3,500 cycles. Fertil Steril. 1998;70(4):638–42. https://doi.org/10.1016/S0015-0282(98)00250-7.

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Published: Aug 11, 2020

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