Randomized controlled trial of the effectiveness of olive and black seed oil combination on pain intensity and episiotomy wound healing in primiparous women: A study protocol

Romina Fili; Fereshteh Behmanesh; Sana Nazmi; Maryam Nikpour; Zahra Memariani

doi:10.1371/journal.pone.0302161

. 2024 May 15;19(5):e0302161. doi: 10.1371/journal.pone.0302161

Randomized controlled trial of the effectiveness of olive and black seed oil combination on pain intensity and episiotomy wound healing in primiparous women: A study protocol

Romina Fili ¹, Fereshteh Behmanesh ^2,^*, Sana Nazmi ¹, Maryam Nikpour ³, Zahra Memariani ⁴

Editor: Ahmed Mohamed Maged⁵

PMCID: PMC11095949 PMID: 38748938

Abstract

Background

Episiotomy is associated with side effects, such as pain and wound infection. Additionally, discomfort after episiotomy affects the quality of life of both the mother and the baby. Medicinal herbs are one alternative method for the treatment of episiotomy wounds. This study will investigate the effectiveness of the combination of olive and black seed oil on pain intensity and the healing of episiotomy wounds in primiparous women.

Methods

This randomized clinical trial will be conducted on primiparous women who have had a normal delivery with an episiotomy. There are 3 groups in this study: one group will receive a combination of olive oil and black seed oil, another group will receive olive oil alone, and the use of oils will start 24 hours after delivery. Ten drops will be applied topically 3 times a day for 10 days. The third group (control) will receive only routine care. Data will be collected through a demographic characteristics questionnaire, REEDA (Redness, Edema, Ecchymosis, Discharge, and Approximation) Scale, and Visual Analog Scale. To determine and compare the effects of pharmaceutical interventions on pain intensity and episiotomy wound healing in the groups, an analysis of variance (ANOVA) test with repeated measurements will be used with SPSS version 22.

Discussion

The results of this study will show the effects of a combination of olive and black seed oil, as well as olive oil alone, on pain intensity and episiotomy wound healing in primiparous women. The positive effects observed in this trial with these oils could be valuable for women who have undergone an episiotomy.

Introduction

Episiotomy is an incision in the area between the perineum and the anus, performed to enlarge the perineum and facilitate the process of natural childbirth, especially in primiparous women [1–3]. The prevalence of episiotomy varies in different countries and races [4]. For example, in Asian countries, due to the anatomical features of the perineum, episiotomy is used as a method to facilitate natural delivery. But there is no inferable statistics of the prevalence of episiotomy in Iran [5]. However, the rate of using episiotomy in a study in Iran was 41.5% [6]. This intervention is associated with side effects such as pain [3, 7, 8]. Studies have shown that approximately 30% of women experience pain in the first two weeks, and 7% experience it up to 3 months after natural delivery [9]. Due to the lack of direct observation of the mother and the proximity of the wound area to the anus, there is a possibility of wound infection [5, 10, 11]. Discomfort after episiotomy affects the quality of life of both the mother and the baby [3, 12, 13]. Considering that the baby requires the mother’s presence and support for growth and development, especially in the early days after birth, it is crucial to pay attention and provide support to mothers who have undergone an episiotomy [10, 14].

Since Iran’s current policy is to increase the birth rate and population, more attention should be paid to prenatal and post-pregnancy care, especially for vaginal childbirth. An unpleasant experience during childbirth can affect a mother’s future pregnancies and may lead to her deciding not to have more children, ultimately reducing population growth [9]. On the other hand, if episiotomy is not used, there is a risk of perineal tears that may cause problems for the mother, such as a reduced quality of sexual life [7, 15] and difficulties with breastfeeding [2, 16]. In Iran, episiotomy is still common, with a prevalence of over 41% among primiparous women [17].

To alleviate the pain intensity of episiotomy and facilitate its faster healing, various treatment methods, including oral, rectal, and sitz baths, are used [14, 18]. Given the increasing prevalence of herbal medicine in recent decades [19] and the adverse effects associated with chemical drugs, such as high costs [7] and mild drowsiness to cardiotoxicity [20], it is advisable to consider herbal medicine, following the recommendations of the World Health Organization [21]. It appears that plant oils, such as olive oil and black seed oil, may be effective in promoting the healing and repair of perineal wounds [21, 22]. According to studies, many medicinal plants, especially olive oil, can accelerate wound healing and reduce pain and complications caused by episiotomy [16, 23]. In a previous study by the author, the use of olive oil sitz baths was found to be effective in reducing pain intensity and promoting episiotomy wound healing in primiparous women [14]. Olive oil is rich in substances that provide it with antimicrobial, antifungal, and anti-inflammatory properties [24, 25]. These include phenolic compounds that promote cell repair, antioxidants that help reduce inflammation, and oleocanthal that can alleviate pain [14, 23, 26]. Moreover, various studies have shown the beneficial effects of olive oil [27], its unsaturated fatty acids, including oleic acid [28], and its phenolic compounds [29] on wound healing. Olive oil has been found effective in treating skin diseases, suppressing the growth of viruses and bacteria, and promoting wound healing [14, 30]. Black seed contains 30% to 40% oil and is particularly rich in a type of antioxidant called thymoquinone [31, 32], as well as phenols, linoleic acid, and oleic acid, which have been the subject of various studies demonstrating their positive effects on wound healing [33]. Additionally, black seed exhibits anti-inflammatory and analgesic properties, along with antiviral and antifungal effects [34, 35]. These effects can be attributed to thymoquinone, which is one of the main constituents of black seed [36]. Thymoquinone is a monoterpene diketone with a molecular weight of 164.204 g/mol and is considered a lipophilic compound [37]. In fact, most of the plant’s properties are attributed to thymoquinone [38]. Studies have shown that black seed is suitable for promoting wound healing in the human body and can help prevent infections [35, 39]. Furthermore, adding black seed oil to olive oil enhances its antioxidant properties [40]. Given the limited number of human clinical studies on black seed oil and the scarcity of research regarding the local effectiveness of the combination of olive oil and black seed oil in alleviating pain and promoting episiotomy wound healing, the present study aims to evaluate the effectiveness of the combination of olive and black seed oil in reducing pain intensity and facilitating episiotomy wound healing in primiparous women. This study will be implemented in Shahid Yahya Nejad Hospital, Babol city. In this hospital, low risk mothers are admitted for delivery. Routine care after episiotomy in these mothers includes sitting in a basin of warm water, and the mothers do not use any oil to repair episiotomy. Recently, some gynecologists prescribe Nivasha spray for faster healing of episiotomy wounds, but these mothers will not be included in the study due to interference with the results of our study. This study adopts a parallel design to compare the side effects caused by drug use, such as burning, itching, episiotomy wound opening, and the need for repair, among 3 groups.

Materials and methods

Study design

This randomized clinical trial will be conducted as a parallel-group, non-inferiority study on postpartum women who have undergone episiotomy in the hospitals of Babol city. The schedule of enrolment, interventions, and assessments was shown in Fig 1. The research design is based on the interpretive standards of trial reports (Fig 2). This study was approved by the Ethics Committee of Babol University of Medical Sciences (code: IR.MUBABOL.REC.1401.145). Additionally, the study protocol was registered in the Iranian Registry of Clinical Trials (code: IRCT20180218038783N2) (S1 File). All methods will be performed in accordance with the relevant guidelines and regulations, including the Declaration of Helsinki, and written informed consent will be obtained from all participants. The trial results will be communicated to participants, health care professionals, the public, and other relevant groups, as well as researchers and sponsors, through the publication of results and reporting in results databases. The SPIRIT Checklist has been shown in S1 Checklist.

Eligibility criteria

Women interested in participating in the study will be invited. After explaining the research objectives and obtaining written informed consent, the researcher will proceed with convenient sampling. Then, based on the inclusion criteria, the samples will be randomly divided into two intervention groups and one routine care group.

Inclusion criteria are primiparous women, natural vaginal delivery with episiotomy, literacy, and BMI < 30. Exclusion criteria are unwillingness of participants to continue participating in the study, fourth-degree tear, history of dermatitis, history of allergy and eczema diagnosed related to plants, and history of gestational diabetes and overt diabetes.

Study sample and sampling

The required sample size was estimated to be 36 based on a previous study on pain intensity of episiotomy using G Power software. The effect size (mean difference) was determined to be 1.4 (pain intensity of episiotomy between the intervention and control groups), with an α of 0.05 and a β of 5% [20].

The researcher will select the samples according to the inclusion criteria and randomly allocate them into 3 groups of 36 individuals using a random-numbers table. The block size will be 6, and the table will be managed by a researcher who is not involved in the sampling process. The person responsible for sampling (a midwifery student) will receive the intervention code from the managing researcher after selecting the sample based on the inclusion criteria. To blind the random allocation list, a unique code will be assigned to each of the intervention groups, known only to the herbal pharmacist associate. The supervisor, researcher, and statistical analyst will be blinded to ensure proper management. To ensure the reliability of this research, the person who examines the episiotomy wound on the first and tenth days will be the same for all mothers. A skilled and trained midwifery student will collect the data by examining the mothers.

Data collection and management

This research will be conducted after obtaining permission from the Ethics Committee of Babol University of Medical Sciences, registering with the Iranian Registry of Clinical Trials, and obtaining the necessary sampling permits. After contacting the midwifery department of the hospitals affiliated with Babol University of Medical Sciences, the researcher invites eligible women to participate in the study. The researcher will first explain the study’s purpose and the nature of the intervention to the women. The researcher ensures the confidentiality of their information, clarifies her responsibility for any treatment complications, and assures them that the treatment interventions will not change if they choose not to participate. Participants are then requested to provide written consent. Additionally, participants are assured that they can withdraw from the study at any stage. Subsequently, the researcher (a midwifery student) informs the supervisor about the sample’s inclusion in the study, and the supervisor shares the intervention code with the researcher.

All study subjects will be educated on following post-delivery health tips and caring for episiotomy wounds. The intervention groups (one group receiving olive oil plus black seed oil and the other receiving olive oil alone) will also receive instructions on how to use the containers containing the oils. Women in the intervention groups will use the oils 24 hours after delivery, applying 10 drops topically 3 times a day for 10 days. Given that each milliliter contains 15 drops, and mothers are required to use the oils 3 times a day, approximately 30 mL of each type of oil will be provided to mothers for the duration of 10 days.

The participants will be instructed to wash and dry their perineum before applying the oils. They should then wear gloves and slowly apply 10 drops of oil to the perineum, massaging it in with their hands. The control group will receive only routine care. All mothers will be provided with painkillers as needed. The type and number of painkillers used by each group will be recorded using a checklist completed by the mother over 10 days. This data will be evaluated and considered as an auxiliary variable in the final analysis. All mothers will be examined again on the 10th day after delivery to determine the severity of pain and healing of the episiotomy wound.

In this research, 3 questionnaires will be administered within the first 24 hours and 10 days after delivery.

Demographic Characteristics Questionnaire: This questionnaire comprises 22 questions that gather information such as age, education level, place of residence, employment status, height, weight, number of pregnancies and abortions, duration of hospitalization during labor, receipt of antibiotics during labor and post-delivery, and hospitalization of the baby in the intensive care unit. The questionnaire was designed based on the research objectives to identify potential confounding variables.
Visual Analog Scale for Measuring Episiotomy Pain Intensity: The Visual Analog Scale, also known as the McGill Pain Ruler, is a linear scale used for pain assessment. It consists of a 10-cm ruler, with 0 indicating no pain and 10 indicating the most severe pain possible. Between these 2 endpoints, the scale is divided into 3 levels: mild pain (1–3), moderate pain (4–7), and severe pain (8–10) [41]. Perineal pain intensity refers to the pain experienced by mothers in their perineal area and is self-reported before and after the intervention.
The Redness, Edema, Ecchymosis, Discharge, and Approximation Scale: The REEDA (Redness, Edema, Ecchymosis, Discharge, and Approximation) Scale is a standardized tool for assessing episiotomy wound healing, including variables such as swelling, bruising, discharge, redness, and the distance between the 2 edges of the episiotomy wound. Each of these variables is scored on a scale from 0 to 3. The researcher records the scores for each variable separately after observing and examining the patient both before and after the examination. The overall score on the scale ranges from 0 to 15, with higher scores indicating less favorable wound healing and lower scores indicating better wound healing. In a reliability analysis conducted by Alvarenga et al. (2015), the kappa coefficient was reported for this scale. The results indicated good agreement for the variable of redness (0.46 < Kappa ≥ 0.66), marginal to good agreement in the first 3 assessments of edema (0.16 < Kappa ≥ 0.46), marginal agreement in the evaluation of ecchymosis (0.25 < Kappa ≥ 0.42), and good agreement in the assessment of the discharge item (0.75 < Kappa ≥ 0.88) [42].

The primary outcomes of this study include the assessment of pain intensity in the episiotomy area and the evaluation of episiotomy wound healing. Secondary outcomes include the monitoring of symptoms such as burning and itching, as well as the occurrence of episiotomy opening and the need for painkillers. These secondary outcomes will be assessed through a combination of examinations conducted by the researcher and self-reports provided by the mothers. Additionally, any side effects reported by each participant will be carefully reviewed, and the total number of side effects within each group will be documented.

The product used in the study is a combination of cold-pressed black seed oil and standard extra-virgin olive oil, both of which adhere to national standards. The standard extra-virgin olive oil is manufactured by a pharmaceutical-grade company called Pishgaman Chemi, while the cold-pressed black seed oil is obtained from the pharmaceutical company Barij Essance. These two oils are mixed in equal proportions [43]. Importantly, both products meet approved specifications in terms of microbial and pollution control, as well as chemical and physical standards. The process of mixing and packaging these two oils is conducted under hygienic conditions within the traditional pharmacy laboratory of the Faculty of Traditional Medicine.

Data analysis

The analysis method used in this study is intention-to-treat analysis, ensuring the maintenance of the random allocation process.

All analyses will be conducted using SPSS version 22, including both descriptive and analytical analyses. A comprehensive outline of the analysis procedures will be documented in the statistical analysis plan.

Descriptive information will be presented using means and SDs or as numbers and percentages. To assess the correlation between quantitative variables, Pearson’s correlation test will be used, while the chi-square test will be used to examine the correlation between 2 qualitative variables.

For comparing pain intensity and episiotomy wound healing after the intervention in the 3 groups, the analysis of covariance (ANCOVA) test will be used, taking into account the measurements taken prior to the intervention. Multilevel linear regression will be conducted to adjust for confounding variables, including demographic, midwifery, and delivery-related factors.

Additionally, the effect size will be demonstrated through mean differences and 95% CIs. A significance level of P < 0.05 will be considered as the threshold for statistical significance.

Report

Researchers will enhance their interaction with individuals to ensure comprehensive data collection. To achieve this, we will establish more robust communication channels with the participants via social media and phone to provide medication reminders.

In this process, one of the researchers (RF) will assume responsibility for data collection, while another individual (SN) will be tasked with entering the data into the SPSS software. A data manager (MN) will review all the data without knowledge of the treatment allocations. These procedures will be conducted under the supervision of FB.

Discussion

This study aims to investigate the effectiveness of a combination of olive and black seed oil on pain intensity and episiotomy wound healing in primiparous women. Olive oil is known for its rich content of substances that impart antimicrobial, antifungal, and anti-inflammatory properties [24, 25], including peniphenol that promotes cell repair, antioxidants that help reduce inflammation, and oleocanthal that suppresses pain [14, 23, 26]. Black seed oil, on the other hand, contains 30% to 40% oil and is particularly rich in thymoquinone, a type of antioxidant [31, 32], along with phenols, linoleic acid, and oleic acid, which various studies have shown to be effective in wound healing [33]. Studies have shown that black seed oil is suitable for wound healing in the human body and can prevent infection [35, 39]. Moreover, combining black seed oil with olive oil enhances its antioxidant properties [40].

Skin wound healing is a critical physiological process that involves the collaboration of various cell types and their products. The repair process begins early in the inflammatory phase, leading to the replacement of specialized structures through collagen deposition and regeneration, which involves cell proliferation and subsequent differentiation from existing tissue cells [44].

While the individual effects of black seed oil [21] and olive oil [9, 14] on episiotomy have been evaluated in previous studies, this research conducted by the study team is the first to examine the combined impact of these 2 oils on episiotomy. Clinical research on whether topical application of this oil combination can effectively promote episiotomy repair and alleviate perineal pain severity is limited. If the results of this study show that the combination of these 2 substances is indeed effective in reducing episiotomy pain intensity and enhancing healing, it could be proposed as a cost-effective treatment option. One of the major limitations of the current study is that some mothers may not return on the 10th day due to the recovery or because of hospitalization of the baby and another limitation is that sterile tape won’t be used and visual inspection will be used in the assessing of wound healing.

Conclusion

The results of this study will show the effects of the combination of olive oil and black seed and olive oil alone on pain intensity and episiotomy wound healing in primiparous women. The potential positive outcomes from testing these oils may propose a viable solution for the use of low-risk methods after childbirth.

Supporting information

S1 Checklist. SPIRIT 2013 checklist.

(PDF)

pone.0302161.s001.pdf^{(126KB, pdf)}

S1 File

(PDF)

pone.0302161.s002.pdf^{(350.5KB, pdf)}

Acknowledgments

The authors would like to thank the Deputy of Research and Technology of Babol University of Medical Sciences and mothers who will participate in this study.

Funding Statement

This study was financially supported by Babol University of Medical Sciences. Award Number: 724134467. F.B will receive the fund.URL: https://www.mubabol.ac.ir/ This funder contributed to the approval of the study. There was no additional external funding received for this study.

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PLoS One. doi: 10.1371/journal.pone.0302161.r001

Decision Letter 0

Eunice Bolanle Turawa

30 Nov 2023

PONE-D-23-34640Randomized controlled trial of the effectiveness of olive and black seed oil combination in pain intensity and episiotomy wound healing in primiparous women: study protocolPLOS ONE

Dear Dr. Fereshteh Behmanesh,

Improve the general outlook of the protocol by restructuring sentences, make your statement clear and logical to enable your readers understand your work. Also, attend to incomplete sentences to use of words.
Make protocol succinct and avoid repetitions.
The "Material and methods" section can be structured to reflect the following:

Study design
Eligibility criteria
Study sample and sampling
Data collection and management
Data analysis
Report

Authors can then resubmit the protocol for review.

Please submit your revised manuscript by Jan 14 2024 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:

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If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

We look forward to receiving your revised manuscript.

Kind regards,

Eunice Bolanle Turawa, MSc

Academic Editor

PLOS ONE

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2. Thank you for stating in your Funding Statement:

"This study was financially supported by Babol University of Medical Sciences. Award Number: 724134467. F.B will receive the fund.

URL: https://www.mubabol.ac.ir/

This funder contributed to the approval of the study."

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Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:

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URL: https://www.mubabol.ac.ir/

This funder contributed to the approval of the study."

Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

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Additional Editor Comments:

Study protocol." This is a clinical trial involving first-time mothers in early postpartum period. The protocol requires general restructuring for clarity, ease communication flow, and scientific soundness. Incomplete and unclear sentences should be improved on. Also, make the protocol succinct without repetitions.

Attachment

Submitted filename: PONE-D-23-34640 et 22Nov 2023 .pdf

pone.0302161.s003.pdf^{(1.6MB, pdf)}

PLoS One. 2024 May 15;19(5):e0302161. doi: 10.1371/journal.pone.0302161.r002

Author response to Decision Letter 0

7 Dec 2023

Dear editor

PLOS ONE

Thank you and the honorable Reviewer (s) for your valuable comments for the manuscript entitled: Randomized controlled trial of the effectiveness of olive and black seed oil combination on pain intensity and episiotomy wound healing in primiparous women: study protocol (PONE-D-23-34640). These comments are very useful in the scientific improvement of the manuscript. Responses to the following comments are given:

1. Improve the general outlook of the protocol by restructuring sentences, make your statement clear and logical to enable your readers understand your work. Also, attend to incomplete sentences to use of words.

Regards, corrected.

2. Make protocol succinct and avoid repetitions.

These items have been corrected and marked in the text with track changes.

3. The "Material and methods" section can be structured to reflect the following:

Study design

Eligibility criteria

Study sample and sampling

Data collection and management

Data analysis

Report

Sincerely, corrected.

4. 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'.

Done

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'.

Done

An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

Done

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

Corrected.

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

This manuscript meets PLOS ONE's style requirements, including those for file naming.

2. Thank you for stating in your Funding Statement:

"This study was financially supported by Babol University of Medical Sciences. Award Number: 724134467. F.B will receive the fund.

URL: https://www.mubabol.ac.ir/

This funder contributed to the approval of the study."

Please include your amended Funding Statement within your cover letter. We will change the online submission form on your behalf.

Corrected

3. Thank you for stating the following in the Acknowledgments Section of your manuscript:

"The authors would like to thank the Deputy of Research and Technology of Babol University of Medical Sciences for supporting the project."

Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:

"This study was financially supported by Babol University of Medical Sciences. Award Number: 724134467. F.B will receive the fund.

URL: https://www.mubabol.ac.ir/

This funder contributed to the approval of the study."

The Acknowledgments Section corrected: The authors would like to thank the Deputy of Research and Technology of Babol University of Medical Sciences and mothers who will participate in this study.

Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

The amended statements was included in the cover letter.

This is a protocol study and data availability are not applicable. This sentence is included in the manuscript and cover letter.

I emailed to plosone@plos.org with a request to remove the direct billing option.

6. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section.

Corrected. It deleted from declarations.

I removed it from the original protocol and uploaded an updated version upon resubmission.

Corrected based on Supporting Information guidelines.

Attachment

Submitted filename: Response to reviewers.docx

pone.0302161.s004.docx^{(17.6KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0302161.r003

Decision Letter 1

Eunice Bolanle Turawa

4 Jan 2024

PONE-D-23-34640R1.

Randomized controlled trial of the effectiveness of olive and black seed oil combination on pain intensity and episiotomy wound healing in primiparous women: Study protocol.

Dear Dr. Behmanesh,

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. Be sure the entire manuscript undergoes thorough editing, focusing on grammar, spelling, and typo errors. It is advisable you use English expert services. We anticipate your revised manuscript and appreciate your attention to these details.

Please submit your revised manuscript by Feb 18 2024 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,

Eunice Bolanle Turawa, MSc

Academic Editor

PLOS ONE

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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

Reviewer #3: 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: No

Reviewer #2: No

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Dear Author

The manuscript has valuable results but needs essential edition as below:

1- English writing is poor. There are a lot of spelling and grammar errors and editing by a native speaker is necessary.

2- In the introduction:

• The mention that not performing an episiotomy leads to severe tearing is not true in all mothers and depends on the case.

• In reference number 6, the sentence is incomplete.

• Start sentence with “such as” is unusual.

3- In the methods section:

• First, the type of study and then the work method should come.

• Objectives should be removed from the beginning of the methods section.

• In reliability and validity of Reeda tool, please wright the number of reliability and validity.

• In inclusion criteria: the sentence is incomplete.

4- Discussion:

• Discussion need to an essential revision.

• According to the results, conclusion need revision.

References:

• Some references should be changed basis on guideline format.

• Revise the reference list according to Paper Submission Guide: Abstract the name of journals.

• More references should be covering the last 5 years.

Be succesful

Reviewer #2: Thank you as you invited me to review this manuscript. Please see my comments as follows:

First of all this study has some grammatical and typo errors and should be revised by an expert person in English literature.

Abstract:

1. Method: While one group will receive olive oil plus black seed and one group will receive olive oil alone, why the third group do not receive placebo, and they will receive routine care?

Introduction

1. The second point of "highlight" should be revised, as the main reason for using herbs is their safety and not the high costs of pharmaceutical treatment.

4. Please use the results of those studies that used olive oil for reducing pain intensity after episiotomy in the introduction.

Methods

1. Women who do not use the oil regularly is not exclusion criteria, but they should consider drop-out.

2. Please move the objectives of the study to the end of introduction.

3. Some of exclusion criteria are drop-out that happen during study such as "women who do not use olive oil regularly"

4. Authors stated that they excluded fourth degree tears. Is that mean you will recruit second and third degree tears?

5. Please provide more details about intervention, e.g. what should participants do before applying the oil on the perineum, any washing?

6. Please write how much oil will be given to each participant?

7. The midwife or a gynecologist that perform episiotomy and type of repair are important factors that did not mention by authors in this study.

8. Authors should advise participants to take the similar pain killers.

9. A significance level of 0.05 will be considered in all tests. It should be <0.05.

Reviewer #3: This is an interesting study looking at the effect of olive oil and black seed on improving on pain intensity and

episiotomy wound healing in primiparous women. This is an inferiority study.

Some comments where the details reported could be clarified further.

1. As this a non-inferiority study, the sample size is missing some fundamental information, i.e what was defined as the clinical minimal difference that would constitute non-inferior. Type 1 error information should be included in sample size calculation. In addition as this is a 3 arms trial, is the non-inferiority hypothesis in relation to control vs EACH intervention, make this comparison explicit and define this.

2. For the randomisation process, please indicate the allocation ratio. No need to state the "The size of the blocks is 6, and 18 blocks of 6 are produced to create a sequence of size 108". You could just state, variable block size. And perharps include this here " (One group, olive oil plus black seed oil and another group of olive oil alone) and control group is routine care"

3. Unsure what this sentence means "The supervisor, researcher and statistical analyst will be blinded to perform proper management." Do you mean blinded analysis?

4. Define primary outcome, i.e pain intensity- how is this measured? How will healing be measured?

5. Same comment for Secondary outcomes, how will these be defined?

6. Define what you mean by intention to treat analysis, i,e people analysed according to the group there were assigned regardless of taking allocated intervention.

7. More information in the analysis section, i.e mention that data will be reported to CONSORT guidelines as this an RCT.

8. In the analysis section as this an RCT, no need to carry out formal tests on baseline characteristics as this not recommended, since any differences would occur by chance. Also mention that all details regarding analysis will be stated in the statistical analysis plan.

9. What is justification of using multi-level modelling? I.e what are the repeated measures of random effect variable?

10. How will adherence/compliance be assessed?

**********

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: No

Reviewer #2: Yes: Parvin Abedi

Reviewer #3: No

**********

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PLoS One. 2024 May 15;19(5):e0302161. doi: 10.1371/journal.pone.0302161.r004

Author response to Decision Letter 1

15 Jan 2024

Dear Editor in Chief

PONE-ONE

Thank you for your thorough review and consideration of our manuscript “Randomized controlled trial of the effectiveness of olive and black seed oil combination on pain intensity and episiotomy wound healing in primiparous women: Study protocol" (PONE-D-23-34640R1) that was submitted to the PONE-ONE.

We believe that the comments and suggestions that were recommended by the reviewers have informed a much improved and more fully developed paper that will offer an important contribution to the field. We have highlighted the changes that were undertaken in response to your comments in the revised manuscript. Responses to each of your comments are below.

Thanks for your kind attention to the manuscript.

Sincerely, Corresponding author

Dr Fereshteh Behmanesh

Reproductive Health

Reviewers Response

Reviewer 1

The manuscript has valuable results but needs essential edition as below:

1- English writing is poor. There are a lot of spelling and grammar errors and editing by a native speaker is necessary. Thank you very much for the opinion of the respected reviewer, according to the suggestion of dear reviewer, this manuscript will be edited by a native and the certificate will be sent for Journal.

2- In the introduction:

• The mention that not performing an episiotomy leads to severe tearing is not true in all mothers and depends on the case. Corrected, p 3, par 1

In reference number 6, the sentence is incomplete. Corrected, p 3, par 2

Start sentence with “such as” is unusual. Corrected, p 4, line 1 & p10, par 3

In the methods section:

• First, the type of study and then the work method should come. First, the type of study and then the work method writhed. P 5, par 2

Objectives should be removed from the beginning of the methods section. Removed and the third objective added in the end of introduction. P 5, par 1

• In reliability and validity of Reeda tool, please wright the number of reliability and validity. Corrected. P 8 & 9

In inclusion criteria: the sentence is incomplete. Corrected. P6, par 2

Discussion:

• Discussion needs to an essential revision. In the protocol study, considering that the findings are not clear, the discussion cannot be written in detail. However, it was corrected according to the comment of the respected referee.

According to the results, conclusion need revision. Corrected. P11, par 2

References:

• Some references should be changed basis on guideline format.

• Revise the reference list according to Paper Submission Guide: Abstract the name of journals.

• More references should be covering the last 5 years. Corrected based on guideline format.

Reviewer 2

First of all this study has some grammatical and typo errors and should be revised by an expert person in English literature. Thank you very much for the opinion of the respected reviewer, according to the suggestion of dear reviewer, this manuscript will be edited by a native and the certificate will be sent for Journal.

Abstract:

1. Method: While one group will receive olive oil plus black seed and one group will receive olive oil alone, why the third group do not receive placebo, and they will receive routine care? This is a very good question. By the way, the research team had also thought about this issue. But since the use of any oil may have a positive or negative effect on wound healing, for this reason placebo was not used in the control group.

Introduction 1. The second point of "highlight" should be revised, as the main reason for using herbs is their safety and not the high costs of pharmaceutical treatment. With respect to the reviewer’s comment, corrected. P 3

2. Authors stated that if not using the episiotomy, there is a perineal tears that may cause problem for mother. Non-indicated episiotomy causes many problems for mother such as sexual dysfunction and pain. Please mention the rate of episiotomy especially non-indicated in Iran. With respect to the reviewer's comment, unfortunately, the incidence of non-indicated episiotomy in Iran was not found in our search. Perhaps because if an episiotomy is non-indicated, the doctor or midwife will not report it due to legal claims.

The following sentence was used instead: In Iran, episiotomy is still common and its prevalence is reported in more than 41% of primiparous women.

3. Please be careful and exact when you are talking about side effects of medications. After delivery, women just receive an analgesic for reducing their pain and analgesics are not expensive and also do not have many side effects. Thanks to the reviewer, this sentence was removed. Of course, in Iran, in addition to painkillers, most doctors routinely prescribe antibiotics after delivery with episiotomy.

4. Please use the results of those studies that used olive oil for reducing pain intensity after episiotomy in the introduction. Added. P4, par 2

Methods

1. Women who do not use the oil regularly is not exclusion criteria, but they should consider drop-out. While thanking the respected reviewer, since our analysis method is ITT, the women should consider drop-out based on reviewer comment. This exclusion criteria were written incorrectly in the manuscript and has now been removed. P 6

2. Please move the objectives of the study to the end of introduction. Removed and the third objective added in the end of introduction. P 5, par 1

3. Some of exclusion criteria are drop-out that happen during study such as "women who do not use olive oil regularly" While thanking the respected reviewer, since our analysis method is ITT, the women should consider drop-out based on reviewer comment. This exclusion criteria were written incorrectly in the manuscript and has now been removed. P 6

4. Authors stated that they excluded fourth degree tears. Is that mean you will recruit second and third degree tears? Yes, that is right. We will recruit second- and third-degree tears.

5. Please provide more details about intervention, e.g. what should participants do before applying the oil on the perineum, any washing? Provided. The samples were asked to wash and dry their perineum before using oils. Then wear gloves and slowly pour 10 drops of oil on the perineum and massage with hands. P 8, par 1

6. Please write how much oil will be given to each participant? Considering that each cc contains 15 drops and mothers should use oils three times a day, approximately 30 cc of each type of oil was given to mothers for 10 days. P 8, par 1

7. The midwife or a gynecologist that perform episiotomy and type of repair are important factors that did not mention by authors in this study. The type of repair will be evaluated by questionnaire but the midwife or a gynecologist that perform episiotomy will not be checked. However, in the author's previous study, this issue was investigated and had no effect on the results of the study.

8. Authors should advise participants to take the similar pain killers The type of painkiller and its number per day in three groups is evaluated by a checklist that is completed by the mother within ten days and then evaluated and considered as auxiliary variable in the final analysis.

9. A significance level of 0.05 will be considered in all tests. It should be <0.05. corrected

Reviewer 3

This is an interesting study looking at the effect of olive oil and black seed on improving on pain intensity and episiotomy wound healing in primiparous women. Some comments where the details reported could be clarified further.

Thank you very much for the comments of the respected reviewer

According to the suggestion of dear reviewer. Sample size corrected

3. Unsure what this sentence means "The supervisor, researcher and statistical analyst will be blinded to perform proper management." Do you mean blinded analysis? As in this sentence: the statistical analyst does not know about the study groups and it will be determined after the statistical analysis (only the pharmacist knows)

4. Define primary outcome, i.e pain intensity- how is this measured? How will healing be measured? The measurement of pain intensity and wound healing is written in detail in the subtitle of "data collection and management" of the method section in paragraphs 5 and 6.

According to the suggestion of dear reviewer, definition of pain intensity and wound healing was added.

The intensity of perineal pain is the pain that mothers feel in their perineal area and it is recorded by self-report method before and after the intervention.

Skin wound healing is an essential physiological process that consists of the cooperation of many cell strains and their products. Attempts to repair the lesion caused by local invasion begin very early in the inflammatory phase. Finally, they lead to repair, which involves the replacement of specialized structures caused by collagen deposition and regeneration, which is related to the process of cell proliferation and posterior differentiation through cells already present in tissue cells.

5. Same comment for Secondary outcomes, how will these be defined? The primary outcomes are pain intensity in the episiotomy area and healing of episiotomy wound. The secondary outcomes are Burning and itching and episiotomy opening and the need for painkillers which will be evaluated through examination by the researcher and through mother's self-report.

6. Define what you mean by intention to treat analysis, i,e people analysed according to the group there were assigned regardless of taking allocated intervention. We will use intention-to-treat analysis in this study, because intention-to-treat analysis will provide an unbiased estimate of the efficacy of the intervention at the level of adherence in the study.

7. More information in the analysis section, i.e mention that data will be reported to CONSORT guidelines as this an RCT.

Statistical analysis according to CONSORT guidelines was written.

9. What is justification of using multi-level modelling? I.e what are the repeated measures of random effect variable? Multilevel linear regression will be done for adjust confounders variables (demographic, midwifery and delivery). In the section of statistical analysis was added and repeat measurement analysis was removed.

10. How will adherence/compliance be assessed? Multilevel linear regression will be done for adjust confounders variables (demographic, midwifery and delivery).

• 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'.

Attachment

Submitted filename: Response to Reviewers 25-10-402.docx

pone.0302161.s005.docx^{(27.3KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0302161.r005

Decision Letter 2

Ahmed Mohamed Maged

23 Feb 2024

PONE-D-23-34640R2Randomized Controlled Trial of the Effectiveness of Olive and Black Seed Oil Combination on Pain Intensity and Episiotomy Wound Healing in Primiparous Women: A Study ProtocolPLOS ONE

Dear Dr. Behmanesh,

==============================

ACADEMIC EDITOR: Please respond to all reviewers comments

==============================

Please submit your revised manuscript by Apr 08 2024 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.

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We look forward to receiving your revised manuscript.

Kind regards,

Ahmed Mohamed Maged, MD

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

Reviewer #3: Yes

Reviewer #4: Partly

Reviewer #5: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Reviewer #3: Yes

Reviewer #4: No

Reviewer #5: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

Reviewer #3: Yes

Reviewer #4: No

Reviewer #5: Yes

**********

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

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

**********

6. Review Comments to the Author

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #3: All comments have been addressed.

Reviewer #4: Dears

• Report rate of episiotomy in Iran?

• In the introduction: Explain setting of the study and how used type of oil therapy people (primiparous) based on culture.

• There are many confounding variables which must be controlled. In Iranian hospitals, the most childbirth is performed by gynecological assistants or midwifery students, with many interventions; confounding variables: for example, time and type of Epi repair, the number of cutgut chromic sutures, Length and depth of episiotomy. fetal information: fetal weight, fetus position of the occiput posterior or anterior, labor information: duration of the first and second stage, removal of the placenta by hand and etc.

• Isn’t report the type of random allocation process.

• How will adherence/compliance be assessed?

• How many times a day were used the oils?

• Was it used based on individual demand and then will be recorded.

• Isn’t report Reliability this research.

• From the ethical point of view, all three groups should have received painkiller, it should be reported which group used less.

• Report of side effect essential oils?

• when Intensity pain and wound healing will be measured?

• How Intensity pain and wound healing will be measured? in REEDA scale for evaluate items; sterile tapes should be used to mark the amount of bruising and redness and... then measure with a ruler.

• Limitation? For example, this primiparous they change our location during first days, Especially the tenth day, from the mother's house to her house and they are not present at the previous address.

Sincerely

Reviewer #5: Thank you very much for giving me the opportunity to review this manuscript.

I congratulate the authors for the work done.

I don't have comment.

**********

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Reviewer #3: No

Reviewer #4: No

Reviewer #5: No

**********

PLoS One. 2024 May 15;19(5):e0302161. doi: 10.1371/journal.pone.0302161.r006

Author response to Decision Letter 2

6 Mar 2024

Dear Editor

PONE-ONE

Thanks for your kind attention to the manuscript.

Sincerely, Corresponding author

Dr Fereshteh Behmanesh

Reproductive Health

Reviewers Response

Reviewer #3:

All comments have been addressed. Thank you very much for your valuable comments in the previous review.

Reviewer #4

1-Report rate of episiotomy in Iran? Thank you very much for the attention of the honorable reviewer, rate of episiotomy in Iran added to the introduction. (P4, Par 2)

2- In the introduction: Explain setting of the study and how used type of oil therapy people (primiparous) based on culture.

Corrected (P 6)

There are many confounding variables which must be controlled. In Iranian hospitals, the most childbirth is performed by gynecological assistants or midwifery students, with many interventions; confounding variables: for example, time and type of Epi repair, the number of cutgut chromic sutures, Length and depth of episiotomy. fetal information: fetal weight, fetus position of the occiput posterior or anterior, labor information: duration of the first and second stage, removal of the placenta by hand and etc. You are absolutely right. But as you know, not all interfering factors can be controlled in studies. One of the ways to reduce the effect of these interfering factors is random sampling, which will be considered in this study. However, many of these factors are investigated by the research team.

Isn’t report the type of random allocation process. Thanks to the accuracy of the reviewer, it was corrected (P8, Par 3).

How will adherence/compliance be assessed? In this study, we will examine the adherence of the samples to drug use and side effects. As mentioned in the method, the use of medicine, painkillers and complications of the intervention will be recorded by the mothers within ten days by means of a designed checklist. Also, during two to three phone calls, in these ten days, they are emphasized about the use of oils. (p11, par 2)

How many times a day were used the oils? Oils will be used 3 times a day (p9, par 2)

Was it used based on individual demand and then will be recorded. After explaining the objectives of the research, any mother who is willing to participate in the study and meets the inclusion criteria will be included. The number of mothers who don’t like to participate in this study, will be recorded.(p9, par 1)

Isn’t report Reliability this research. Reliability of this research added to the method. To ensure the reliability of this research, the person who examines the episiotomy wound on the first and tenth days will be the same for all mothers.(p 8, par 4)

From the ethical point of view, all three groups should have received painkiller, it should be reported which group used less. Thank you very much for your accuracy, you are absolutely right. This was written in the manuscript. All three groups can use painkillers. Also, people report how many painkillers they used in ten days by self-reporting through a checklist provided to them. This is mentioned in the method. (p 9, par 3)

Report of side effect essential oils? The side effects of essential oils will be assessed and reported. This is mentioned in the method. (p 11, par 2)

when Intensity pain and wound healing will be measured? In the first 24 hours after delivery, and ten days later. This corrected in the method. (p9, the last paragragh)

How Intensity pain and wound healing will be measured? in REEDA scale for evaluate items; sterile tapes should be used to mark the amount of bruising and redness and... then measure with a ruler. Pain intensity will be measured by VAS based on mother’s self-reporting. About REEDA scale, You are right. But because of the limitations of using sterile tapes in our research, we will use visual inspection.

Limitation? For example, this primiparous they change our location during first days, Especially the tenth day, from the mother's house to her house and they are not present at the previous address. On the 10th day, mothers will be gone to the women's clinic of the hospital for examination. (On the 10th day, gynecologists routinely examine mothers' sutures. Therefore, the address of the mother is not important for us. But one of the major limitations of the current study is that some mothers may not return on the 10th day due to the recovery or because of hospitalization of the baby. This restriction was added to the end of the discussion.

Reviewer #5:

Thank you very much for giving me the opportunity to review this manuscript.

I congratulate the authors for the work done.

I don't have comment. Thank you very much for your valuable comment.

• 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'.

fereshteh-834

21Aban139322

Attachment

Submitted filename: Response to Reviewers2.docx

pone.0302161.s006.docx^{(18KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0302161.r007

Decision Letter 3

Ahmed Mohamed Maged

22 Mar 2024

PONE-D-23-34640R3Randomized Controlled Trial of the Effectiveness of Olive and Black Seed Oil Combination on Pain Intensity and Episiotomy Wound Healing in Primiparous Women: A Study ProtocolPLOS ONE

Dear Dr. Behmanesh,

Please submit your revised manuscript by May 06 2024 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'.

We look forward to receiving your revised manuscript.

Kind regards,

Ahmed Mohamed Maged, MD

Academic 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:

==============================

ACADEMIC EDITOR: Please respond to all reviewers comments

==============================

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

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #4: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

Reviewer #4: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Reviewer #4: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

Reviewer #4: Yes

**********

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

Reviewer #4: Yes

**********

6. Review Comments to the Author

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #4: Dear authors

Thank you for your revises. Please correct these two comments as well:

• you record:the number of the painkiller used during 10 days.

• you add in the limitations that to assess wound healing, sterile tape was not used and visual inspection was used.

Sincerely, Reviewer #4

**********

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 #4: No

**********

PLoS One. 2024 May 15;19(5):e0302161. doi: 10.1371/journal.pone.0302161.r008

Author response to Decision Letter 3

26 Mar 2024

Dear Editor

PONE-ONE

I review the reference list to ensure that it is complete and correct.

Sincerely, Corresponding author

Dr Fereshteh Behmanesh

PhD in Reproductive Health

Reviewers Response

Reviewer #4

Dear authors

Thank you for your revises. Please correct these two comments as well:

• you record: the number of the painkiller used during 10 days.

Many thanks for your valuable comments. Corrected. P 9. Par 3

• you add in the limitations that to assess wound healing, sterile tape was not used and visual inspection was used.

With many respects to you, this sentence added to the limitation. P 14, par 3

Attachment

Submitted filename: Response to Reviewers 4.docx

pone.0302161.s007.docx^{(14.6KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0302161.r009

Decision Letter 4

Ahmed Mohamed Maged

28 Mar 2024

Randomized Controlled Trial of the Effectiveness of Olive and Black Seed Oil Combination on Pain Intensity and Episiotomy Wound Healing in Primiparous Women: A Study Protocol

PONE-D-23-34640R4

Dear Dr. Behmanesh,

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.

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Kind regards,

Ahmed Mohamed Maged, MD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

PLoS One. doi: 10.1371/journal.pone.0302161.r010

Acceptance letter

Ahmed Mohamed Maged

26 Apr 2024

PONE-D-23-34640R4

PLOS ONE

Dear Dr. Behmanesh,

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team.

At this stage, our production department will prepare your paper for publication. This includes ensuring the following:

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on behalf of

Professor Ahmed Mohamed Maged

Academic Editor

PLOS ONE

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

S1 Checklist. SPIRIT 2013 checklist.

(PDF)

pone.0302161.s001.pdf^{(126KB, pdf)}

S1 File

(PDF)

pone.0302161.s002.pdf^{(350.5KB, pdf)}

Attachment

Submitted filename: PONE-D-23-34640 et 22Nov 2023 .pdf

pone.0302161.s003.pdf^{(1.6MB, pdf)}

Attachment

Submitted filename: Response to reviewers.docx

pone.0302161.s004.docx^{(17.6KB, docx)}

Attachment

Submitted filename: Response to Reviewers 25-10-402.docx

pone.0302161.s005.docx^{(27.3KB, docx)}

Attachment

Submitted filename: Response to Reviewers2.docx

pone.0302161.s006.docx^{(18KB, docx)}

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Submitted filename: Response to Reviewers 4.docx

pone.0302161.s007.docx^{(14.6KB, docx)}

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PERMALINK

Randomized controlled trial of the effectiveness of olive and black seed oil combination on pain intensity and episiotomy wound healing in primiparous women: A study protocol

Romina Fili

Fereshteh Behmanesh

Sana Nazmi

Maryam Nikpour

Zahra Memariani

Roles

Abstract

Background

Methods

Discussion

Introduction

Materials and methods

Study design

Fig 1. The schedule of enrolment, interventions, and assessments.

Fig 2. CONSORT (Consolidated Standards of Reporting Trials) flow diagram.<.

Eligibility criteria

Study sample and sampling

Data collection and management

Data analysis

Report

Discussion

Conclusion

Supporting information

Acknowledgments

Funding Statement

References

Decision Letter 0

Eunice Bolanle Turawa

Roles

Author response to Decision Letter 0

Decision Letter 1

Eunice Bolanle Turawa

Roles

Author response to Decision Letter 1

Decision Letter 2

Ahmed Mohamed Maged

Roles

Author response to Decision Letter 2

Decision Letter 3

Ahmed Mohamed Maged

Roles

Author response to Decision Letter 3

Decision Letter 4

Ahmed Mohamed Maged

Roles

Acceptance letter

Ahmed Mohamed Maged

Roles

Associated Data

Supplementary Materials

ACTIONS

PERMALINK

RESOURCES

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