Variation in Anti-Mullerian Hormone Levels with Age in Women Accessing In Vitro Fertilization Services in Ghana
Round 1
Reviewer 1 Report
Mawusi et al., in a prospective cohort study, explored the association between serum AMH levels and maternal age in infertile Ghana females undergoing IVF treatment. The manuscript is adequately presented. However, it does not deliver a new message to reproductive endocrinologists' specialists in other countries than Ghana. The manuscript's added value is exploring (in a prospective design) the functional ovarian reserve, represented by serum AMH levels, in different age groups of Ghanaian women undergoing IVF treatment. However, in doing so, the authors do not try to compare or speculate on any differences with other ethnicities or races. This is a crucial remark that should be explored and explained. In addition to that, I have other comments:
1. Although the cohort (by definition) explored only women undergoing IVF treatment, it includes women up to 55 years of age; this point should be explained.
2. It is not clear whether this cohort included women with PCOS. All women had regular menstruation, but some had high AMH levels in the PCOS range. The PCOS issue is brought up in the discussion section but not in the materials and methods or results. If PCOS were included, they should have a separate analysis. If not, this should be mentioned in the material and methods.
3. The etiology of the recruited infertile women undergoing IVF should be added.
4. To prevent batch-to-batch inconsistencies in serum AMH levels determination and to reach definite conclusions in the study, it is advised to freeze all serum taken from all participants and conduct the analyses simultaneously after completion of the study. This was not accomplished and ought to be added as another limitation.
5. Strangely, only 1% of participating women below 30 had a serum AMH level below 2.19 ng/mL. In naturally distributed infertile cohorts, the rate of women with low ovarian reserve or poor ovarian response is much higher. This should be clarified.
6. Please clarify whether a Helsinki committee approval was received and whether signed informed consent was obtained from every participating woman.
Author Response
Response to the comments by Reviewer 1
Mawusi et al., in a prospective cohort study, explored the association between serum AMH levels and maternal age in infertile Ghana females undergoing IVF treatment. The manuscript is adequately presented. However, it does not deliver a new message to reproductive endocrinologists' specialists in other countries than Ghana. The manuscript's added value is exploring (in a prospective design) the functional ovarian reserve, represented by serum AMH levels, in different age groups of Ghanaian women undergoing IVF treatment. However, in doing so, the authors do not try to compare or speculate on any differences with other ethnicities or races. This is a crucial remark that should be explored and explained. In addition to that, I have other comments:
Response. We thank the Reviewer for this important comment. In this study, the study participants were all Ghanaians (same race). However, we have discussed this in the discussion section
- Although the cohort (by definition) explored only women undergoing IVF treatment, it includes women up to 55 years of age; this point should be explained.
Response: We thank the Reviewer for bringing out this important point. In this study, some of the women who reported for IVF were up to 55 years and they were included as well.
- It is not clear whether this cohort included women with PCOS. All women had regular menstruation, but some had high AMH levels in the PCOS range. The PCOS issue is brought up in the discussion section but not in the materials and methods or results. If PCOS were included, they should have a separate analysis. If not, this should be mentioned in the material and methods.
Response: In this study women with PCOS were excluded. We have revised the Methods and also discussed it in the Discussion
- The etiology of the recruited infertile women undergoing IVF should be added.
Response: We thank the Reviewer for this comment. In this study, women the specific etiologies of infertility of the recruited women we not included. This has been stated as a limitation of the study.
- To prevent batch-to-batch inconsistencies in serum AMH levels determination and to reach definite conclusions in the study, it is advised to freeze all serum taken from all participants and conduct the analyses simultaneously after completion of the study. This was not accomplished and ought to be added as another limitation.
Response: We thank the Reviewer for this suggestion. We agree with the reviewer on this point. We have added this point in the discussion as a limitation of the study as suggested by the Reviewer.
- Strangely, only 1% of participating women below 30 had a serum AMH level below 2.19 ng/mL. In naturally distributed infertile cohorts, the rate of women with low ovarian reserve or poor ovarian response is much higher. This should be clarified.
Response: We agree with the Reviewer on this point. However, the study population is not the normal distribution of women. These are women who have infertility, and their characteristics may be different from the general population of women. We have interrogated this further in the discussion.
- Please clarify whether a Helsinki committee approval was received and whether signed informed consent was obtained from every participating woman.
Response: We thank the Reviewer for this point. We obtained Helsinki committee approval and the study participants provided written informed consent prior to the study. We have stated this point in the manuscript.
Reviewer 2 Report
I read with great interest the manuscript, which falls within the aim of this Journal. In my honest opinion, the topic is interesting enough to attract the readers’ attention. Nevertheless, authors should clarify some points and improve the discussion, as suggested below.
Authors should consider the following recommendations:
- Manuscript should be further revised in order to correct some typos and improve style.
- To date many efforts are spent to identify a correct algorithm which considers woman's age and ovarian reserve markers as a tool to optimize the recombinant follicle-stimulating hormone (rFSH) starting dose in IVF procedure. Nevertheless, current available evidence regarding PCOS women, particularly the ones with high AMH, does not seem adequate. I would be glad if the authors discuss this important point, referring to: PMID: 30242498; PMID: 30607593
Author Response
Response to the comments by Reviewer 2
I read with great interest the manuscript, which falls within the aim of this Journal. In my honest opinion, the topic is interesting enough to attract the readers’ attention. Nevertheless, the authors should clarify some points and improve the discussion, as suggested below.
Authors should consider the following recommendations:
- Manuscript should be further revised in order to correct some typos and improve style.
Response: We thank the reviewer for this comment. We have revised the manuscript and corrected all the typos.
- To date many efforts are spent to identify a correct algorithm which considers a woman's age and ovarian reserve markers as a tool to optimize the recombinant follicle-stimulating hormone (rFSH) starting dose in IVF procedure. Nevertheless, current available evidence regarding PCOS women, particularly the ones with high AMH, does not seem adequate. I would be glad if the authors discuss this important point, referring o: PMID: 30242498; PMID: 30607593
Response: We thank the Reviewer for this important point and for referring us to relevant articles to improve our manuscript. We have revised the discussion and referenced the articles suggested.
We have attached the revised version of our manuscript
Round 2
Reviewer 1 Report
The answer to comment number one is not satisfactory. IVF in women above 45 years of age is considered worldwide an ineffective treatment. Please elaborate on how many women were above 45 years of age, their percentage of the total cohort, and how many oocytes were retrieved.
As well, the answer to comment number 5 is not satisfactory. The percentage of low ovarian reserve in infertile women is usually similar to that in the general population. The authors are advised to describe more accurately the inclusion criteria of the recruited women for their study.
It is advised to add the number of the Helsinki committee approval.
Author Response
- The answer to comment number one is not satisfactory. IVF in women above 45 years of age is considered worldwide an ineffective treatment. Please elaborate on how many women were above 45 years of age, their percentage of the total cohort, and how many oocytes were retrieved.
Response: We thank the reviewer for enquiring further about the women who were above 45 years. We did further analysis based on the request of the reviewer. There were 28 (6.8%) women who were above 45 years [median age 47.5 years (IQR=0.59)] and their median AMH levels were 2.2 ng/ml (IQR=0.55). We have included the in the results section as well.
We have already indicated in the limitations that we did not include IVF outcomes including the number of oocytes retrieved because of the unavailability of that data
- As well, the answer to comment number 5 is not satisfactory. The percentage of low ovarian reserve in infertile women is usually similar to that in the general population. The authors are advised to describe more accurately the inclusion criteria of the recruited women for their study.
Response: We appreciate the comment made by the reviewer. We have revised the inclusion criteria. As we state we included all the women who presented for IVF services and consented to take part in the study. Further detail on the inclusion and exclusion criteria have been stated in the Methods. At this point, we will appreciate it if there are any further additions or recommendations from the reviewer to improve this section
- It is advised to add the number of the Helsinki committee approval.
Response: We have included the ethics approval number in the manuscript
