Title: IS HYSTEROSALPINGO-FOAM SONOGRAPHY (HyFoSy) MORE TOLERABLE
IN TERMS OF PAIN AND ANXIETY THAN HYSTEROSALPINGOGRAPHY (HSG)? A
PROSPECTIVE REAL-WORLD SETTING MULTICENTRE STUDY
Version: 1 Date: 03 Dec 2021
Reviewer's report:
Interesting topic on which a few studies have been published, however the study is limited by
its small sample and design.
1. What does a real-world setting/study mean? Never heard of it, isn’t it a prospective cohort
study (with a more pragmatic approach)?
2. The authors use the term HyCoSy, but they state they use ExEm-FOAM as contrast, then it’s
called HyFoSy instead of HyCoSy. Please clarify.
3. Abstract – Results: “HyCoSy shows higher tolerability to both: pain and anxiety.” And “ A
great difference was observed in state anxiety between the two groups;” This is interpretation
of the results, please just state the results. Interpretation should be part of the conclusion.
4. Introduction: “Sixty per cent of cases are related to female sterility”, isn’t the percentage a bit
lower? Approximately 30% male infertility, 30% female and 30% unexplained? Please check.
5. Introduction: “Finally, some studies have shown an increase in the rate of post-procedure
gestation (18)(19)(20)(21).” There is way more literature supporting the statement for HSG
instead of HyFoSy/HyCoSy. The fertility enhancing effects of HyFoSy/HyCoSy are still
unclear.
6. I miss some literature/studies from Ludwin and colleagues in the introduction and discussion
section. Furthermore, I miss the study of van Rijswijk and colleagues on an RCT comparing
HyFoSy and HSG.
7. Method: Why Sept 2017 until October 2018?
8. Method: “The epidemiological characteristics of the patients are collected in Table 1”, this
phrase needs to be part of your results section.
9. Method: I feel the choice for this setting/design needs to be part of the introduction, not in
the methods.
10. Method: “This condition prevents randomisation of the study.”, please remove this
statement. It is a prospective study, completely different than an RCT.
11. Methods: IRB approval was granted, please state number and place of approval.
12. Methods: Was the study prospectively registered? Please state the protocol number.
13. Methods: step 1 WHO Pain Ladder drug 1, could you provide a reference?
14. Methods: Heavy genital bleeding? Please change into heavy menstrual bleeding.
15. Methods: Please state a reference for the VAS scores, and the scores are in centimetres, 0cm
to 10cm.
16. Methods: was an HSG only performed by a nurse? Not by a gynaecologist or fertility
specialist?
17. Methods: Endovaginal, I would suggest the term “transvaginal”.
18. Why Visipaque?
19. Pelvic active infection? Do you mean a PID?
20. Were all women entering the fertility clinics for HSG/HyFoSy recruited? Were there any
women who refused participation? I cannot find them in your manuscript or flowchart?
21. Discussion: I would suggest to make your discussion more succinct. Maybe start with a
sort summary, followed by the strengths/limitations and the implications. I feel a few things a
explained multiple times in the discussion.
22. Table 1: I find the table a bit difficult to read, maybe change the P-values to a new column
on the right? I miss some baseline characteristics: age, ethnicity, LETTZ/conisation? Could you
maybe provide these?
23. What was the definition of sterility/infertility? I cannot find the baseline characteristics on
duration of infertility etc? And did all women have consecutive ART?
24. Figure 1: I find it a bit difficult to read, for your analysis you used 82 versus 107 women?
But your flowchart ends with different numbers due to failed procedures. I would suggest to
adjust your flowchart to make it easier to read.