Introduction

Recent advancements in three-dimensional (3D) printing technology have facilitated the production of 3D printed models of exemplary quality. Continued reductions in operating costs and time to generate 3D printed models has increased feasibility and gained considerable interest from the medical field. 3D printed models can be scaled to size, and display fine details, closely resembling human anatomy. As a result, there is an increasing body of literature reporting on the clinical applications of 3D printing in medicine.

In high-fidelity 3D printing protocols, segmentation software is used to convert high quality 2-dimensional (2D) Magnetic Resonance (MR), Computed Tomography (CT) or ultrasound (US) images to 3D digital models, which can then be printed [1]. Hence, 3D printed models have the ability to be patient specific, with clinical applications in personalized medicine. In gynecology, 3D printed models can depict patient-specific female pelvic anatomy and gynecologic pathology, which may benefit physicians, trainees, and patients in their understanding of complex disease and management options.

With a growing body of literature in the area of 3D printing, there has been a need to summarize the data on 3D printing and develop clinical recommendations for its use. Systematic reviews have outlined the applications of 3D printing in surgery, identifying advantages including, better visualization of anatomy for pre-operative planning, improved operative outcomes, and decreased surgical time [2, 3]. As well, there have been studies which have reviewed the uses of 3D devices within specific surgical specialties such as orthopedics, spinal surgery, neurosurgery, plastics, and urology [4,5,6,7,8]. However, challenges in summarizing the data has been reported [9] such that the overall efficacy and effectiveness of 3D printed models across medical specialties remains unknown due to the breadth of uses, lack of comparable hypotheses, and non standardized reporting of outcomes across the literature [9].

Objectives

A broad range of clinically meaningful applications for 3D printing in gynecology have been identified in the literature. The primary objective of this study is to systematically report the clinical applications of individualized 3D printing in gynecology. Additional objectives will be to summarize the production process for printing patient specific 3D printed models and determine the feasibility of personalized 3D printing in gynecology. We have chosen to use a scoping review to summarize our data, considering the challenges with performing systematic reviews on the topic of 3D printing in medicine [9] and mainly related to the heterogeneity of relevant studies.

Methods

Eligibility criteria, information sources, search strategy

A systematic review of the published literature was conducted to evaluate the uses of 3D printing in gynecology. Inclusion criteria consisted of publications up to and including 31 May 2021, of all study designs, which were published in English, had a gynecologic context and involved production of patient specific 3D printed models. Publications involving 3D imaging alone, without patient-specific 3D model production; where 3D printing was used for bioprinting, scaffolding, tissue engineering; or where 3D printing was used in a purely obstetrical context (i.e for fetal imaging, investigating fetal pathology), were excluded.

Four medical databases (Medline, Embase, CENTRAL, Scopus) and grey literature were searched using search terms which included “3D printing,” “gynecology” and relevant anatomic structures (vagina, cervix, uterus, fallopian tubes, ovaries, pelvic floor, ureters, urethra) or derivatives of these terms (Supplementary Material).

Study selection

Studies were manually screened and assessed for eligibility by two independent reviewers, (CC, TF) initially by title and abstract review and subsequently by full text review.

Data extraction

All data from studies selected for inclusion was extracted using a pre-established data extraction form. Disagreements between reviewers regarding study screening, eligibility, and data extraction were settled through discussion and consensus between the reviewers. Screening and data extraction was performed using the online platform Covidence. The study followed PRISMA protocol for scoping reviews [10].

Assessment of risk of Bias

NA

Data synthesis

The primary outcome was clinical applications of individualized 3D printing in gynecology. Additional outcomes assessed were 1) the production process used for producing 3D printed models (software, 3D printer, printing materials), 2) measures of feasibility (3D printing costs, production time). A descriptive approach for data synthesis was used.

Results

Study selection

Our search yielded 4102 studies, of which 990 duplicates were removed, leaving 3112 studies to be screened. Title and abstract screening was performed by the reviewers leaving 120 studies for assessment of full text for eligibility. Eighty-eight studies were excluded for the following reasons: models were not patient specific (52), articles were duplicates (17), not the correct patient population (8), models were not printed (7), not in English (2), non-human models (1), and/or could not be accessed (1). In total 32 studies were included for review. PRIMSA flowchart can be seen in Fig. 1.

Fig. 1
figure 1

PRISMA flowchart

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Study characteristics

Of the 32 studies reviewed, 13 (41%) were case series, 12 (38%) were case reports, 4 (13%) were cohort studies, 2 (6%) were controlled trials (1 randomized and 1 non randomized) and 1 (3%) was a retrospective study. Nineteen studies (59%) were full text articles and the remaining 13 (41%) were conference abstracts. Studies were carried out in 13 different countries, with the most common places being China (9), The United States (6) and Canda (4). Studies were performed from 2014 to most recent. Most studies (21, 66%) printed 5 or less models. Seven studies (22%) printed greater than 5, (up to 50 models) and 4 (13%) studies did not specify the number of models produced. Additional study characteristics can be seen in Tables 1 and 2.

Table 1 Study characteristics
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Table 2 3D-printed model production specifics
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Risk of bias

NA

Synthesis of results

Primary outcome

Clinical applications and impact of personalized 3D printed models

3D printed models were intended for use by physicians (25/32, 78%), both physicians and patients (4/32, 13%), both physicians and trainees (1/32, 3%) or patients (2/32, 6%). Models were used in studies for each of the gynecologic subspecialties including, gynecologic oncology (23/32, 72%), benign gynecology (5/32, 16%), urogynecology (2/32, 6%), pediatric gynecology (1/32, 3%), and reproductive endocrinology and infertility (1/32, 3%). Patient pathologies studied included gynecologic cancer (23/32, 72%), uterine fibroids (3/32, 9%), Mullerian anomalies (2/32, 6%), endometriosis (1/32, 3%), placenta percreta (1/32, 3%), stress urinary incontinence (1/32, 3%), and infertility (1/32, 3%). In 20 (63%) studies, the patient specific 3D printed models being produced were brachytherapy templates/cylindrical applicators; in 10 (31%) studies they were anatomical models; and in 2 (6%) studies they were other medical devices. Specific 3D printed models produced in each study can be seen in Table 1.

Secondary outcomes

3D printed model production and feasibility

Data sources used for production of the 3D printed models included: MRI (14/32, 44%), CT (7/32, 22%), both MRI and CT (5, 16%), physical exam (2/32, 6%), trial and error (2/32, 6%) or did not specify (2/32, 6%). Data software, 3D printers and 3D printing materials used varied across studies. The most commonly used 1) data software were Computer Aided Design (CAD) Software (4/32, 13%) and Solidworks (5/32, 16%); 2) 3D printers were Stratasys Fortus (3/32, 9%) and PolyJet J750 (3/32, 9%); and 3D printing material was polylactic acid (5/32, 16%). A large number of studies did not specify data software (12/32, 38%), 3D printer (13/32, 41%), or 3D printing materials (11/32, 34%) used. One study produced a 3D printed mold, from which multiple models could be produced.

3D printing costs were only provided by 2 (6%) studies and production time by 7 (22%) studies. Costs listed per model were $10.94 and $35 USD. Production time varied from 86 minutes to 5 days.

Discussion

With a growing body of literature in the area of 3D printing and continuous advancements in its technology, there has been a need to summarize the data on 3D printing and its clinical applications in medicine. We performed a scoping review to systematically report on the clinical applications of individualized 3D printing in gynecology. Although a review on the role of 3D printing in gynecology has previously been published [13], this study was limited in its reporting of applications for reproductive surgery only. Furthermore, its search was limited to a single platform (Pubmed), yeidling only 11 studies, and lacked information on the feasibility and impact of 3D printing on patient outcomes in gynecology. Here, we present on themes regarding clinical applications of patient specific 3D printing in gynecology, as summarized below.

Medical devices

Brachytherapy is an integral component of the management of both primary and recurrent gynecologic cancers. It facilitates the delivery of a high dose of localizaed radiation to a small volume tumor, while minimizing radiation dose to surrounding normal tissue [42]. To optimize treatment, selection of the most appropriate brachytherapy technique, intracavitary versus interstitial, and applicator, should be individualized based on the depth of invasion, distribution of disease, and patient specific anatomy [43]. A variety of applicator designs and sizes have been developed to limit patient discomfort while enhancing radiation dose distribution [42, 43]. However, still it remains a challenge to find an optimally fitting brachytherapy applicator for each patient’s individual anatomy and pathology [43].

Our scoping review has highlighted that patient specific 3D printed brachytherapy devices have been the most commonly studied individualized 3D printed model in gynecology in the literature to date [19,20,21,22,23, 25, 27, 29, 30, 33,34,35,36,37, 39,40,41, 44]. The 3D printed models produced and studied were mainly personalized vaginal brachytherapy cylinder applicators and or interstitial brachytherapy needle templates in a population of patients with gynecologic malignanies including primary vaginal cancer, locally advanced or recurrent cervical or endometrial cancer [19, 20, 22, 23, 25, 29, 30, 33,34,35,36,37, 39,40,41, 44]. In addition, some studies created 3D printed devices that could be personalized and used in combination with standardized applicators or templates [21, 27].

Some of the larger cohort studies provided clinically relevant results supporting the utility of individualized 3D printed devices for use in brachytherapy treatment of gynecological malignancies. Specifically, Logar et al. (2019) and Yuan et al. (2019) report increased radiation doses to the target volume and decreased dose to organs at risk, in patients with gynecologic malignancies previously treated with external beam radiation, when 3D printed individualized 1) vaginal applicators and 2) guidance templates, respectively, were used for brachytherapy treatment, in comparison to standardized devices [22, 39]. Similarly, 3D printed individualized brachytherapy trans-vaginal template/applicator +/− transperineal template facilitated high dose parameters, a high response rate (84.4% 1 month after completion), with no severe complications, in of a group of patients with central recurrent gynecologic malignancy in the study by Jiang et al. (2020) [44]. Further, Qu et al. (2021) showed that 3D-printed non-coplanar template (3D-PNCT)-assisted computed tomography (CT)-guided iodine-125 seed ablative brachytherapy could reduce the misalignment error and improve accuracy of needle puncture for non-central pelvic lesions [30].

These studies each used uniquely designed patient specific 3D printed brachytherapy applicators/templates for specific gynecologic oncology patient populations, and altogether suggest significant benefit to their use. Studies which can reproduce these results, and provide long term data on outcomes, while also investigating feasibility may facilitate wider spread use of these devices in a clinical setting in the future.

While the literature regarding the use of patient specific 3D printed personalized devices has been well explored in the context of brachytherapy applicators, there may be further utility of 3D printed personlized medical devices for other purposes. Barsky et al. (2018) showed that a patient specific silicone pessary produced from a 3D printed mold was effective in management of stress urinary incontinence and showed no short term complications [14]. Authors from another study, which was however excluded from this review due to it’s obstetrical context, similarly used 3D printing to produce a patient specific cervical cerclage pessary [45]. Unique utility was additionally shown by Pavan et al. where an individualized 3D printed vaginal mold was used by a patient with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome following McIndoe modified vaginoplasty, as a permanent dilator post-operatively promoting return to sexual function [26].

This scoping review has outlined excellent examples of patient specific medical devices in gynecology, including brachytherapy applicator/templates, pessaries, and a vaginal dilator. Other studies have presented approaches and assessed the feasability of using 3D printing to introduce multiple shapes and sizes of various gynecologic devices such that variations in patient anatomy can be better accomodated for. Examples include connector tubing for dilatation and evacuation [46], intrauterine balloons for management of post partum hemorrhage [47], vaginal speculums [48], and drug eluting intravaginal rings [49,50,51,52,53,54]. When applicable, create patient specific devices using 3D printing can have an even greater potential for best fit, which can improve their effectiveness and patient experience. Hence efforts should be made to continue to create, produce, and study personalized devices in gynecology further. Some challenges to the widespread production and use of patient specific devices are related to cost and time burden of production, and the requirement of approval from health regulatory bodies. But, larger studies showing effectiveness and safety may help to overcome some of these limitations.

Surgical planning

Studies have also suggested a role for individualized 3D printed models for surgical planning. As initial proof of this concept, Ajao et al. and Mackey et al. produced high fidelity individualized 3D printed models which were shown to accurately represent gynecologic pathology (i.e endometriotic nodules or fibroids) in relation to the surrounding tissues, and closely correlated with patient anatomy at the time of surgery [11, 24].

Additional studies have outlined the the utility of patient-specific 3D printed models for surgical planning and intraoperative assistance further [12, 13, 16, 17, 31, 32] In preparation for benign gynecologic procedures, Flaxman et al. (2020) found that that the use of patient-specific 3D-printed models altered the surgeons’ perception of surgical difficulty, perceived risk for surgical complications, and planned hemostatic techniques, and increased their confidence in their pre-operative plan [17] and Chen et al. (2017) showed that the models decreased operative time and blood loss [16]. Baek et al. (2016) and Sayed Aluwee et al. (2017) reported that gynecologic oncologists had an increased comprehension of patient anatomy and pathology (eg. tumor size, shape, borders) [12, 32], and increased confidence in route of excision [12], with use of individualized 3D printed models, in preparation for oncologic surgeries. Finally, Barbosa et al. (2019) reported that patient specific 3D printed models provided novel information and assisted in planning of infertility procedures, including hyperoscopic myomectomy, septoplasty and embryo transfer, and assessment of ovarian reserve in preparation for IVF [13].

Overall, these studies highlight that in preparation for complex gynecologic procedures, across gynecologic subspecialties, personalized 3D printed models may provide additional infomation to the surgeon regarding patient specific anatomy and pathology, greatly assisting in the development of their surgical plan. While theoretically, with better preparation for the surgical procedure, it seems that there is the potential for the models to help to reduce complications and improve outcomes, none of the studies in this review were able to provide evidence to support this. Hence, studies are needed to further investigate surgical outcomes related to the use of patient specific 3D printed models for surgical planning to provide clearer evidence to the benefit of their use.

Two studies have also shown benefit of 3D printed patient specific models for brachytherapy planning [15, 38]. In these studies, 3D printed patient specific models were effective and non invasive for pre-planning brachytherapy in patients with cervical cancer [15, 38]. Physicians using the models, reported high fidelity and usefulness, and their overall evaluation of the cervical cancer model was 8.0 ± 0.8 points [38].

Education

Personalized 3D printed models have also been investigated as an educational tool. In one study, patient specific 3D models of Mullerian anomalies were found to increase gynecologists’ understanding of Mullerian anomalies and their confidence in surgical correction [18]. There is also evidence that they may help to promote patient education [12, 32, 38]. Patients report greater understanding of their disease and radiotherapy treatment or surgical intervention with the assistance of the 3D printed models [12, 32, 38].

The literature regarding the utility of patient specific 3D printed models for educational purposes in this scoping review appears limited. However, during our review of the literature, we did note that there is more significant data regarding the use of non-patient specific 3D printed models in education in gynecology [55,56,57]. Unfortunately, these were excluded from our scoping review due to the non-patient specific nature of the 3D printed models. This has idenitified a need for a furture study to summarize the literature regarding 3D printing overall, inclusive of both patient specfic and non-patient specific models, for the purposes of trainee education in gynecology.

Methodological considerations

Our study has identified a need for larger, higher quality studies and more consistent reporting on the topic of individualized 3D printing in gynecology. The majority of the studies in this scoping review were case reports or small case series which were proof of concept pilot studies. These studies have provided strong evidence that we now have the technology to produce patient specific 3D printed models in gynecology, and that there are many great uses possible. However, unfortunately the workflow process for production of the personalized 3D printed models including software, 3D printer, and materials used, as well as measures of feasibility, such as cost, and time for production were widely under-reported. As a result, reproducibility of these studies is limited. Further, the true feasibility of personalized 3D printed models remains unknown, as measures of feasibility were mainly unreported. Further, when they were reported, for example, cost per model of $10.94 and $35 USD, is misleading, as this does not account for the costs of the printer itself, and payment of the team who are needed to assist in preparing images for 3D printing. Further production time again was mainly unreported or else highly variable and non specific.

Finally, while the studies in this scoping review suggest clinical benefit to the use of patient specific 3D printed models, the data to support this was scant. Again, there was a focus on the ability to produce patient specific 3D printed models, but minimal data providing evidence to their impact on patient outcomes. In order for personalized 3D printing to be used in a widespread fashion in gynecology and supported by our heathcare system, we need studies which provide cost-to-benefit analysis and which provide evidence of their ability to improve patient outcomes. Hence, we are putting out a call for larger, experimental studies with clear and consistent reporting of feasibility measures on the topic of personalized 3D printing in gynecology, which will provide us with the data we need to promote their ongoing utility in this specialty.

Conclusion

Overall, this study has highlighted that there are a number of studies on the topic of personalized 3D printing in gynecology currently available. Through our scoping review we have summarized the literature to date on the topic of personalized 3D printing in gynecology and outlined many novel and potentially practice changing uses across gynecologic subspecialties. Some of these uses have included personalized applicators/templates for brachtherapy in the management of gynecologic malignancies, and other customized medical devices, as well as patient specific models for surgical planning and patient and trainee education.