PONE-D-22-12329Pharmacotherapy of infertility in Ghana: Why do subfertile couples discontinue their fertility treatment?PLOS ONE

Dear Dr. Arhin,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. In addition to comments provided by the two reviewers, the please consider the following:

Line 26: Consider revision to "The study employed an exploratory qualitative design"

Line 26-26: It is enough to say "purposive sampling technique"

Line 28: Write ‘8’ in word

Line 29: Consider changing "were sampled and interviewed" to just "were interviewed"

In the abstract, state the data analysis approach in a short sentence.

Line 32: Consider revising to: “The major reasons for discontinuation of infertility medical services included….”

Line 37-39: It might be better to say the insight provided rather that say it will provide insight. The current statement sounds like a justification for the study, not a recommendation from the findings, as might be the intention of the authors.

Line 94: This initial statement does not make your study population clear. Twenty couples ordinarily means 20 pairs of persons, making 40 persons. Also, please indicate that you did not interview both members of each couple pair, and why not.

Please ensure to remove any personal identifying information from your manuscript, including names of organizations where identifying them is not essential to the information being provided. You must justify the inclusion of names that identify any entity.

Concerning your suggestions on the approach to data collection, infertility is a sensitive issue and FGD may still not be the most appropriate fora for data collection, particularly when the proposed participants are currently experiencing infertility.

In line with the comments of one of the reviewers, consider removing the word "subfertile" from your title.

Do pay attention to typographical and grammatical errors.

Please submit your revised manuscript by Jul 22 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Olujide Arije

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at 

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and 

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf.

2. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. 

In your revised cover letter, please address the following prompts:

a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.

We will update your Data Availability statement on your behalf to reflect the information you provide.

3. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: N/A

Reviewer #2: N/A

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: No

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This is an interesting paper which focuses specifically on pharmacotherapy for sub-fertile couples in Ghana and why these couples may discontinue treatment before achieving pregnancy.

In the title you talk about choices that subfertile couples make, but I am not sure how representative the term couples is of the study population?

Some small changes which would make some things clearer for me:

line 72, pg 4 - change to 'for infertility' instead of 'of infertility'

line 73, pg 4 - add Metropolis to Cape Coast, as you later refer to just 'the metropolis' this confused me, and then you later call it Cape Coast Metropolis

line 76, pg 4 - to enable stakeholders 'to' develop (word missing)

lines 94-96, pg 5 - I would like to see this more clearly, on first reading it appears you interviewed 20 couples, but you then say you interviewed 14 women and 6 men. Maybe be specific that you interviewed 20 clients, which were a combination of 14 women and 6 men - but were any of these couples?

line 130 - pg 7 - who did the transcription? and also did you use a specific type of thematic analysis?

line 132, pg 7 - reword 'two of the authors coded few' this reads as though they coded a minimal amount - might be useful to say how many and which (HCP or clients)

line 135, pg 7 - It feels more accurate to say that themes were identified than that they emerged.

line 138, pg 8 - I think you mean that you were maintaining confidentiality, the opposite to disclosing the identity of the participants?

line 190, pg 10 - 'live' birth (also line 430)

line 433, pg 21 - you talk about internal and external pressures - which do you mean specifically?

line 485, pg 24 - midst, not mist

I really enjoyed reading this, thank you. And I think you have made some really important points, particularly about the abdication of responsibility of the male partners.

There has been much made of the 'delay' to treatment outcomes - do you have a sense, or data to indicate what sort of time frames that are contributing to the drop out of treatment?

I think that this article may need some editing for language and clarity, but the data support the conclusions and suggestions you have made for how services could be improved.

Reviewer #2: Review PONE-D-22-12329

This a very important qualitative interview study on why couples in Ghana discontinue fertility treatment (pharmacotherapy). A topic where we have very limited knowledge from low/middle income countries. Globally, infertility is one of the most frequent diseases among reproductive-aged women and men. In middle and low-income countries the access to fertility treatment is limited and is not affordable for many couples with infertility. The study is carefully conducted, data clearly presented and the manuscript is easy to follow.

I have a number of minor suggestions –

Terminology

I suggest to follow the terminology in the International Glossary on Infertility and Fertility Care, 2017 (Zegers-Hochschild et al., Human Reproduction, 2017). My suggestion is to use “infertility” as this is clearly defined (and not “subfertility” that is usually not well-defined); fertility care, fertility clinics, fertility treatment and in line with this fertility patients.

Throughout the manuscript is used both “clients” and “fertility patients”. I suggest to use only one term (fertility patients). Similarly, is used both “infertility” and “subfertility”. I suggest infertility as stated above.

Introduction

is well-written and provides a good overview. I suggest to include a few more papers on infertility in Sub-Saharan countries. Search e.g., for papers in Pubmed published by Silke Dyer, Johanne Sundby, Florence Naab and others and you will find papers e.g., on access to fertility care, the psychosocial impact of infertility, studies on the impact of male infertility, how fertility patients assess treatment. Some could probably also be included in the Discussion section.

Materials and methods

I suggest to add either a table or a short overall description of the study participants (besides their gender). For the fertility patients – e.g., age range, previous reproductive history (have child/children or not), previous treatment. For the health care professionals – e.g, number of years in fertility care. This info should be provided on a group level, so the study participants could not be identified.

I suggest to put the paragraph on Ethical approval as the last section before Results.

Please, provide a reference to the thematic analysis used.

The description of how you assigned codes to the interview transcripts is not a Result and should be placed in the M&M section.

Results

I suggest you provide a table showing themes from interviews with fertility patients and with health care professionals, respectively. To help the reader to have an overview.

Otherwise the result section is easy to follow and quotes selected are illustrative for the theme.

In quotes, I would recommend not to mention e.g., name of fertility clinics in order not to reveal study participant identity.

I would prefer Psychological distress (p. 15 , line 299) instead of disturbances (which sounds closer to psychiatric disorders).

Discussion is relevant. I found it interesting that the fertility patients’ do not mentioning stigma as a reason for discontinuation, but it was mentioned by the health care professionals. Could this difference be discussed in short?

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Eleanor Molloy

Reviewer #2: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PONE-D-22-12329R1Pharmacotherapy of infertility in Ghana: Why do infertile patients discontinue their fertility treatment?PLOS ONE

Dear Dr. Arhin,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please see "additional Editor comments" section below

Please submit your revised manuscript by Sep 25 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Thomas Tischer

Staff Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments (if provided):

• We noticed that your study included 20 participants, however the "occupation" row in Table 1 adds up to 21 individuals. If it was possible to provide multiple answers to this questions, please indicate this. Otherwise, please ensure to correct the "occupation" row with the correct value
• We noticed that in Table 1 there is a difference in the capitalization of "Male" vs "female"
• Please check your other tables for similar inconsistencies (numbers and grammar)

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: N/A

Reviewer #2: N/A

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: No

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thank you for the work you have done on this manuscript, it is an important field of study and crucial that we are exploring experiences of accessing healthcare across all populations and countries.

Reviewer #2: The authors have carefully revised the manuscript in accordance with comments from reviewers and AE. I have two additional minor comments:

1. Most places the author states "infertile patients" and fewer places "fertility patients" (e.g., Table 3, and in sub-heading line 205). I suggest to be consistent throughout the manuscript and use one term only. As previously mentioned, I prefer "fertility patients"; however, this is not a requirement.

2. I would avoid the term "drop-out" of fertility treatment, as "drop-out" could indicate something that just happened passively. Studies - including your own - clearly indicates that fertility patients who discontinue treatment has been actively through a decision-making process.

On p. 6, Sampling, I suggest e.g. to revise to "20 fertility patients who had discontinued treatment " and in Table 1 to change "drop-out time" to Treatment discontinuation. I am not sure whether it is discontinuation after 1-3 months of being in fertility treatment?

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Eleanor Molloy

Reviewer #2: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Pharmacotherapy of infertility in Ghana: Why do infertile patients discontinue their fertility treatment?

PONE-D-22-12329R2

Dear Dr. Arhin,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

George Vousden

Staff Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: