Application of Additive Manufacturing in Assisted Reproductive Techniques: What Is the Evidence? A Clinical and Technical Systematic Review of the Literature

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This article reviews the transformative role of 3D and bio 3D printing technologies in Assisted Reproductive Technology (ART) to enhance reproductive outcomes. Following a systematic literature review, 48 studies were analyzed, highlighting bio 3D printing's potential in female infertility treatments, such as follicle complex culture and ovary printing. The use of decellularized extracellular matrix (dECM) as bioink shows promise in replicating ovarian environments for in vitro oocyte maturation. Additionally, advancements in endometrial interventions, personalized IVF tools, and educational simulators are explored, demonstrating these technologies' potential to improve precision and success rates in reproductive medicine. This review anticipates future advancements, offering new possibilities for fertility care.

The manuscript is well designed and written in a logical order. The authors have performed a comprehensive analysis and efficiently conveyed their findings. Nevertheless, there are certain inquiries and recommendations that, if taken into consideration, could improve the overall caliber of the manuscript. Below are some comments about this study:

Title

The title is clear and informative, effectively conveying the study's main focus.

 Abstract

The abstract effectively communicates the structure, methodologies, and principal discoveries of the study. The terminology used is technical yet clear, effectively conveying the primary aspects of the experiment.

Introduction

The introduction is well-organized and written.

Results

3.1. Bio-3D printing

3.1.1. Follicle complex culture and ovary printing

It is mentioned that: Both from the application of dECM (19, 20) and hydrogel (21) in animal experiments, very interesting feedback with successful in vitro follicular culture was ob-tained. Of great interest is the work of Hassanpour et al in 2015 who, in addition to animal follicles, tried the 3d culture of human follicles in dECM (22).

Add 2 other studies related to the mentioned study which utilized ovarian decellularized tissue for culture and maturation of preantral follicles and resulted in advanced oocyte maturation and IVF results, an important outcome of ART.

The decellularized ovary as a potential scaffold for maturation of preantral ovarian follicles of prepubertal mice (https://www.tandfonline.com/doi/full/10.1080/19396368.2021.1968542)

3.4. Male factor Infertility

This section is written very briefly and would benefit from further elaboration. Additional studies could be incorporated to provide a more comprehensive and in-depth analysis of the topic. Given the title’s focus on Assisted Reproductive Technology (ART), it is recommended to expand this section to comprehensively address both male and female reproductive aspects. Incorporating studies on ART applications for both sexes would provide a well-rounded perspective, enhancing the depth and relevance of the content.

 

Author Response

Dear Reviewer,

We really appreciate your feedback. After carefully reviewing your comments, please find our responses below.

Comment 1: 

Add 2 other studies related to the mentioned study which utilized ovarian decellularized tissue for culture and maturation of preantral follicles and resulted in advanced oocyte maturation and IVF results, an important outcome of ART.

The decellularized ovary as a potential scaffold for maturation of preantral ovarian follicles of prepubertal mice (https://www.tandfonline.com/doi/full/10.1080/19396368.2021.1968542)

Response to Comment 1:

Thank you for the comment. We have added two more references and added a small explanation in the relevant section. Explanation in the manuscript as follows: "Add 2 other studies related to the mentioned study which utilized ovarian decellularized tissue for culture and maturation of preantral follicles and resulted in advanced oocyte maturation and IVF results, an important outcome of ART.

The decellularized ovary as a potential scaffold for maturation of preantral ovarian follicles of prepubertal mice (https://www.tandfonline.com/doi/full/10.1080/19396368.2021.1968542)"

The references added as recommended by the Reviewer:

"

23. Alaee S, Asadollahpour R, Hosseinzadeh Colagar A, Talaei-Khozani T. The decellularized ovary as a potential scaffold for maturation of preantral ovarian follicles of prepubertal mice. Syst Biol Reprod Med. 2021;67(6):413-427.

24. Pors SE, Ramløse M, Nikiforov D, Lundsgaard K, Cheng J, Andersen CY, Kristensen SG. Initial steps in reconstruction of the human ovary: survival of pre-antral stage follicles in a decellularized human ovarian scaffold. Hum Reprod. 2019;34(8):1523-1535.

"

Comment 2:

"3.4. Male factor Infertility

This section is written very briefly and would benefit from further elaboration. Additional studies could be incorporated to provide a more comprehensive and in-depth analysis of the topic. Given the title’s focus on Assisted Reproductive Technology (ART), it is recommended to expand this section to comprehensively address both male and female reproductive aspects. Incorporating studies on ART applications for both sexes would provide a well-rounded perspective, enhancing the depth and relevance of the content."

 

Response to Comment 2:

Thank you for your comment. We have elaborated on the matter by adding 5 sections, 3.4.1 to 3.4.5. We have also added 3 new references to back up these sections, references 45, 46 and 47.

45. Richer G, Vanhaecke T, Rogiers V, Goossens E, Baert Y. Mouse In Vitro Spermatogenesis on 3D Bioprinted Scaffolds. Methods Mol Biol. 2024;2770:135-149.

46. Salem M, Khadivi F, Javanbakht P, Mojaverrostami S, Abbasi M, Feizollahi N, Abbasi Y, Heidarian E, Rezaei Yazdi F. Advances of three-dimensional (3D) culture systems for in vitro spermatogenesis. Stem Cell Res Ther. 2023;14(1):262.

47. Liu Y, Lin A, Tiersch TR, Monroe WT. A 3D Printed Vitrification Device for Storage in Cryopreservation Vials. Appl Sci (Basel). 2021;11(17):7977. doi: 10.3390/app11177977.

 

Thank you very much for the time and effort you dedicated to our study. For anything else we can do for you, please let us know. 

Reviewer 2 Report

Comments and Suggestions for Authors

·      It would be beneficial to expand on the specific criteria used to include and exclude studies. While you mention the snowball technique for identifying additional relevant papers, providing more detail on the criteria could strengthen the transparency of your review.

·       The discussion on the applications of bio 3D printing in reproductive medicine is insightful. However, consider elaborating on the implications of the findings from the studies included in your review, particularly regarding how these advancements can directly impact patient care and success rates in fertility treatments.

·       The literature search methodology is well-articulated, but it may enhance the review to include a brief summary of the types of studies that were most frequently encountered in your search. This could provide readers with a clearer understanding of the current landscape of research in this field.

·       While the review presents a comprehensive overview of the advancements in additive manufacturing, it may be beneficial to include a section on the limitations of the current research and potential areas for future investigation. This could guide subsequent studies and highlight the ongoing challenges in the field 

Comments on the Quality of English Language

Need improvement

Author Response

Dear Reviewer,

We really appreciate your feedback. After carefully reviewing your comments, please find our responses below.

Comment 1: 

"It would be beneficial to expand on the specific criteria used to include and exclude studies. While you mention the snowball technique for identifying additional relevant papers, providing more detail on the criteria could strengthen the transparency of your review."

Response to Comment 1:

Thank you for your comment. We have amended section 2, Materials and Methods, to further expand on our inclusion and exclusion criteria and how we utilised the snowball technique for reference expansion.

 

Comment 2: 

"The discussion on the applications of bio 3D printing in reproductive medicine is insightful. However, consider elaborating on the implications of the findings from the studies included in your review, particularly regarding how these advancements can directly impact patient care and success rates in fertility treatments."

Response to Comment 2:

Thank you for your feedback. We have amended our Discussion section to better reflect the direct impact on patient care and success rates in fertility treatments based on these advancements.

 

Comment 3:

"The literature search methodology is well-articulated, but it may enhance the review to include a brief summary of the types of studies that were most frequently encountered in your search. This could provide readers with a clearer understanding of the current landscape of research in this field"

Response to Comment 3:

Thank you for your comment. We have expanded in section 2, Materials and Methods, under the Literature Search accordingly to reflect on the types of studies that were most frequently used in order to help readers get a clearer understanding on the current landscape of research in this field.

 

Comment 4:

"While the review presents a comprehensive overview of the advancements in additive manufacturing, it may be beneficial to include a section on the limitations of the current research and potential areas for future investigation. This could guide subsequent studies and highlight the ongoing challenges in the field"

Response to Comment 4:

Thank you for your feedback. We have added a new section, 6. Limitations and Future Directions and have expanded on both the limitations of the current research and the future directions. 

Thank you very much for the time and effort you dedicated to our study. For anything else we can do for you, please let us know.