Novel methods to enhance surgical sperm retrieval: a systematic review

Figures & data

Table 1. PRISMA 2009 checklist

Section/topic	#	Checklist item	Reported on page #
TITLE
Title	1	Identify the report as a systematic review, meta-analysis, or both.	1
ABSTRACT
Structured summary	2	Provide a structured summary including, as applicable: background; objectives; data sources; study eligibility criteria, participants, and interventions; study appraisal and synthesis methods; results; limitations; conclusions and implications of key findings; systematic review registration number.	2
INTRODUCTION
Rationale	3	Describe the rationale for the review in the context of what is already known.	2
Objectives	4	Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS).	2
METHODS
Protocol and registration	5	Indicate if a review protocol exists, if and where it can be accessed (e.g. Web address), and, if available, provide registration information including registration number.	3
Eligibility criteria	6	Specify study characteristics (e.g. PICOS, length of follow-up) and report characteristics (e.g. years considered, language, publication status) used as criteria for eligibility, giving rationale.	3
Information sources	7	Describe all information sources (e.g. databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched.	3
Search	8	Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated.	3
Study selection	9	State the process for selecting studies (i.e. screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis).	3
Data collection process	10	Describe method of data extraction from reports (e.g. piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators.	3
Data items	11	List and define all variables for which data were sought (e.g. PICOS, funding sources) and any assumptions and simplifications made.	3
Risk of bias in individual studies	12	Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis.	3
Summary measures	13	State the principal summary measures (e.g. risk ratio, difference in means).	3
Synthesis of results	14	Describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g. I^2) for each meta-analysis.	-
Section/topic	#	Checklist item	Reported on page #
Risk of bias across studies	15	Specify any assessment of risk of bias that may affect the cumulative evidence (e.g. publication bias, selective reporting within studies).	3
Additional analyses	16	Describe methods of additional analyses (e.g. sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified.	-
RESULTS
Study selection	17	Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram.	Figure 1
Study characteristics	18	For each study, present characteristics for which data were extracted (e.g. study size, PICOS, follow-up period) and provide the citations.	3
Risk of bias within studies	19	Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12).	-
Results of individual studies	20	For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot.	-
Synthesis of results	21	Present results of each meta-analysis done, including confidence intervals and measures of consistency.	-
Risk of bias across studies	22	Present results of any assessment of risk of bias across studies (see Item 15).	-
Additional analysis	23	Give results of additional analyses, if done (e.g. sensitivity or subgroup analyses, meta-regression [see Item 16]).	-
DISCUSSION
Summary of evidence	24	Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g. healthcare providers, users, and policy makers).	10
Limitations	25	Discuss limitations at study and outcome level (e.g. risk of bias), and at review-level (e.g. incomplete retrieval of identified research, reporting bias).	10
Conclusions	26	Provide a general interpretation of the results in the context of other evidence, and implications for future research.	10
FUNDING
Funding	27	Describe sources of funding for the systematic review and other support (e.g. supply of data); role of funders for the systematic review.	12

From: Moher D, Liberati A, Tetzlaff J Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA Statement. PLoS Med 2009;6: e1000097. DOI:10.1371/journal.pmed1000097

For more information, visit: www.prisma-statement.org.

Figure 1. PRISMA flowchart of screening and selection procedure

Figure 2. Seminiferous tubular histology patterns imaged by MPM at low (a and d) and high (b and e) magnification compared to high magnification stained tissue (c and f). Normal spermatogenesis is shown by green areas in A to C and seminiferous tubules with SCO pathology is shown by blue areas in D to F. H&E (c and f). Scale bar represents 500 μm (a and d) and 80 μm (b,c,e,f). Permission for reproduction obtained from Elsevier Publishing, Ramasamy et al. [10]

Figure 3. (a) Mean processed spectra for SCO (red curve) and active spermatogenesis (blue curve) with 1000 and 1690 cm⁻¹ discriminatory Raman peak intensity, respectively. (b) Representative testicular biopsy shows active spermatogenesis. (c) Representative testicular biopsy shows SCO. (b and c) H&E, reduced from ×200. Permission for reproduction obtained from Elsevier Publishing, Osterberg et al. [16]

Figure 4. Comparative FFOCT and H&E-stained histology. (a) Testis of a normal rat shows seminiferous tubules with relatively uniform size and shape, (b) H&E histology stain of the same specimen. Arrows point to the sperm within the tubule lumen. (c) Seminiferous tubules in the testis of a rat treated with busulfan, showing thinner tubules and a greater degree of heterogeneity in size and shape with ~10% normal spermatogenesis. (d) H&E staining of the same specimen. Field of view in each panel: 1 mm² Permission granted under the creative commons attribution license, Ramasamy et al. [19]

Figure 5. Operating room setup with the ORBEYE™ surgical microscope. The microscope coming from the surgeon’s left-frontal side is held over the surgical field resulting in no obstacle between the surgeon and the monitor. The operator, the assistant and the entire operating staff using 3D glasses have the same view as the operator

Table 2. Advantages and disadvantages of different retrieval/identification methods

Retrieval/identification method	Advantages	Disadvantages
Micro-TESE	Good chance of sperm recovery [4]	Risk of damage to testis architecture [7] Success may depend on surgical skill [7]
Multiphoton microscopy	3D in vivo histological images Depth of penetration up to 400 µm Real-time analysis [10] Lower energy laser = minimal damage [11] Decreased operating time	Human studies not conducted to determine risk of genetic damage [13]
Raman spectroscopy	Flexible probe for surgical ease Non-destructive near infrared light source [14]	Safety not assessed in human models Specimen preparation takes 2 minutes and can be influenced by light pollution [17]
Full-field optical coherence tomography	Fast and easy to obtain images [18] Safe light source from 150-W halogen lamp [19]	Absence of cellular details Limited depth of imaging below cellular surface [20] Only images ex vivo specimens [20] Efficacy not proven compared to other techniques [19]
ORBEye	Elimination of eyepieces allows for better surgical posture [21] Simple to use and easy to transport May allow for shorter surgery times [21] Wider FOV and longer DOF eliminates need for frequent repositioning [22] 3D viewing monitors provides optimal teaching/demonstration environment [23]	Cost Surgical assistants have rotated surgical view, which can lead to confusion during operation [24]
Ultrasonography	Fast, easy, portable [28] Widely available [28] Ability to locate areas of high perfusion [33] Help rule out areas of absent spermatogenesis [31] Improve success rates of sperm retrievals [36,37]	Operator dependent [38] Requires training and experience [38] Difficulty with resolving microvasculature of the testicle [31]
Artificial Intelligence	Automated assessment of extracted sperm [37,38,44] Real-time analysis of sperm [37] Ability to work with unstained images [37] High accuracy [37] Ability to predict outcomes prior to extraction [41] Avoid operator dependence [43]	Training phase of AI can be limited by the number of sperm images available [39] Limited by quality of microscopy images [39] Technology is not widely available Requires collaboration between computer scientists and clinicians

FOV: field of view; DOF, depth of field.

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