Uterine Transplantation for Absolute Uterine Factor Infertility: A Systematic Review

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript presented for review is an interesting analysis of the role uterine transplantation has in women with absolute uterine factor infertility. The objectives are well defined yet the overall analysis is a bit lacking in my opinion.

Firstly why limit the search between 2019 and 2024 given the scarcity of cases admited by the authors?

Secondly - the objectives are: To describe the process of donation, transplantation, and subsequent gestation. Yet there is no numerical data provided. The authors should present the studies included in tabelated form providing data about pregnancy rates, live births,  complications during gestation, complications due to immunotherapy,  rejection rate and so on.

Third: while discussing the ethical considerations a special part should be dedicated to inequities of access.  Most centers offering uterine transplantation do not include women over 30 years old. Although this selection of patients is understandable since the technique is still in its infancy and the  results can be negatively affected by including older patients, most women with AUFI are over 30. Also, in the context of current social norm in which women postpone child bearing for a later period in life, deniyng access to these women is controversial. 

Last: a paragraph on the role of uterine transplantation in cancer survivors should be included highlighting potential diferences between this type of patient and a patient with no history of cancer.

Author Response

Dear reviewer,

Thank you very much for your constructive feedback. In response to your comments, we have made the following revisions:

1. We acknowledge your concern regarding the limited timeframe of our search. Our primary reason for this selection was to ensure that the included studies reflect the most recent advancements in uterine transplantation (UTx), as this is a rapidly evolving field. However, given the scarcity of cases, we agree that expanding the search period could provide a more comprehensive overview.
2. We recognize the importance of providing quantitative data to strengthen our analysis. That's the reason why we had include a tabulated summary of the studies reviewed as supplementary file incorporating key outcome measures such as pregnancy rates, live birth rates, complications during gestation, immunosuppressive therapy-related complications, and rejection rates. This enhance the clarity and impact of our findings.

3. Your point regarding the exclusion of women over 30 years old from most UTx programs is highly relevant. While patient selection criteria are primarily guided by the novelty of the technique and its potential success rates, the exclusion of older patients raises important ethical concerns, especially considering the increasing trend of delayed childbearing. We will dedicate a specific section to discussing these inequities in access and their ethical implications.

4. We appreciate this valuable suggestion and acknowledge that cancer survivors represent a unique patient population with specific medical and ethical considerations. We will include a dedicated paragraph discussing the potential differences in outcomes, eligibility criteria, and medical risks for cancer survivors undergoing UTx compared to patients with congenital or acquired uterine factor infertility.

We hope these revisions address your concerns and improve the overall quality of the manuscript. 

Thank you again for your careful consideration of our paper.

Best regards.

Reviewer 2 Report

Comments and Suggestions for Authors • The main question addressed by the research is the systematic review of the uterine transplantation as a treatment of absolute uterine factor infertility adding to the subject ethical considerations.  • The topic is relevant to the field although it does not address a specific gap in the field. • Compared with other published material, it adds to the subject ethical considerations and recipients' perceptions. • The conclusions are consistent with the evidence and arguments presented and they address the main question posed because bioethical principles and other related topics are included in the discussion and the conclusions • The references are appropriate. However, some data about common drugs used in immunosuppression should be mentioned in brief. As an example, oral prednisolone is given for the first days after transplantation. However, in the event of rejection episodes, intravenous methylprednisolone is necessary for the first days. • The figure related to the selection process is useful.

 

This is an interesting study. However, some data about common drugs used in immunosuppression should be mentioned in brief. As an example, oral prednisolone is given for the first  days after transplantation. However, in the event of rejection episodes, intravenous methylprednisolone is necessary for the first  days. 

Author Response

Dear Reviewer,

Thank you for your valuable feedback on our manuscript. We have carefully considered your comments and made the necessary revisions.

We have now incorporated the missing information of immunosuppressive treatment before transfer, during pregnancy till delivery.

Thank you again for your careful consideration of our paper.

Best wishes.

Reviewer 3 Report

Comments and Suggestions for Authors

The manuscript provides a comprehensive review of uterine transplantation (UTx) as a treatment for absolute uterine factor infertility (AUFI), an emerging and impactful area of reproductive medicine. It is well-written, relevant, and grounded in current literature. However, it could benefit from some refinements to enhance its clarity and impact.

The topic is significant and addresses a pressing clinical issue.

That said, it would be great if you can provide:

 

More quantitative data on clinical outcomes (e.g., success rates, complications, live births).

 

Discuss limitations of the included studies (e.g., heterogeneity, short follow-up durations).

 

 

Author Response

Dear Reviewer,

Thank you very much for your thoughtful and constructive feedback on our manuscript. In response to your comments, we have added a section discussing limitations of the included studies, and more data on clinical outcomes.

Thank you again for your careful consideration of our paper.

Kind regards.

Reviewer 4 Report

Comments and Suggestions for Authors

Dear Authors,

I read your paper with great interest. The topic is interesting and is developed in all its points.

To improve the article, I suggest:

-discuss other possible indications for treatment that could be taken into consideration in the future  (such as other uterine anomaly, adenomyosis, Asherman syndrome)

Best Regards

Author Response

Dear Reviewer,

Thank you very much for your insightful comments and guidance. We greatly appreciate the time and effort you have dedicated to reviewing our work.

We have carefully reviewed your suggestions and implemented the requested changes. Specifically, we have included information about another infertility reasons such as abnormal growth of endometrial tissue or uterine resection surgeries, that can be beneficiary of this rising reproductive option.

Best regards.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have addressed my concerns adequately and I believe the manuscript can be published in the current form.