Reviewer's report
Title:A randomised controlled trial of a preconceptional dietary intervention in
women undergoing IVF treatment (PREPARE trial)
Version:2Date:19 May 2014
Reviewer: Marius Meintjes
Reviewer's report:
Overall, this proposed study is one of few in human medicine that will attempt to
address the effect of diet on fertility and, may be, directly on oocyte quality. It has
been known for many years that nutrition during the non-hormone sensitive
stages of follicular development has profound effects on the fecundity and fertility
of farm animals. The sensitivity to nutritional priming of the reproductive system
in humans, before the follicular phase of the reproductive cycle, has been
neglected for many years. In my opinion, this is a very much needed study,
addressing the potential effects of essential nutrients including the often
neglected time period before hormone-dependent follicular development.
1. Will the study design adequately test the hypothesis?
The study design should be able to test the hypothesis.
2. Are sufficient details provided to allow replication of the work or comparison
with related analyses: if not, what is missing?
The essential details, doses and end points are provided to allow a replication of
this study.
3. Does the manuscript adhere to the relevant standards for reporting and data
deposition: if not, in what ways?
In my opinion, this manuscript adheres to the relevant standards for reporting
and data deposition.
4. Is the writing acceptable?
Well written with a few small typographical errors:
• Background – third line: Delete “on” before “IVF outcomes”.
• Background – last sentence, first paragraph: Delete “on” before “embryo
quality”.
• Background – third paragraph, last sentence: Consider defining EPA and DHA
when used first in the text.
Recommended revisions:
Discretionary Revisions
• We know that the effect of body mass can be significant on oocyte quality and
pregnancy outcomes. The BMI range proposed seems to be unnecessary broad.
Any attempt to reduce the impact of patients as a source of variation may aid in
the power of this study. I suggest to reduce the allowable BMI range for this
study to be closer to 22-30 kg/m2. This should not have a significant impact on
available study subjects.
• Consider to proactively stratify for fertilization method. When performing ICSI,
the premature stripping of cumulus cells may significantly effect possible
last-minute cumulus-oocyte nutrient transfer.
• Consider to proactively stratify for patient age groups, or alternatively if the
potential number of study recruits allow, narrow the inclusive age range to
exclude older patients, providing for a more uniform study group.
• Exclude patients not using ejaculated sperm, i.e., epididymal and testicular
sperm. This may disproportionately affect the primary end point.
• Confirm and ensure that only a single stimulation protocol is used. What steps
are taken to ensure that stimulation is as standardized as possible?
• Are you providing for physician effect?
• Consider including the males in your study by asking them to take the same
treatment as their partners and comparing the stated pre-study semen
parameters with the semen parameters at the time of fertilization.
Minor Essential Revisions
Please correct the few typographical errors noted under 4. above.
Major Compulsory Revisions
None.
In my opinion, this study protocol is worthy of publication. Encouraging further
nutritional studies like this before the event of follicular growth will be valuable,
not only for the benefit of infertile couples, but may also be applicable to the
larger population.
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests.