Studies which are not well designed produces misleading results concerning the CO₂ pneumoperitoneum impact on postsurgical ovarian function

We read with great interest the article by Qin et al. (1). because the physiological aspects of pneumoperitoneum belong to our research subjects (2,3). Although we congratulate the authors for the randomized trial, it seems that their study design and results are raising several questions. The authors studied postsurgical complications, ovarian function (mean ovarian volume, maximal ovarian volume, mean follicle number, and maximal follicle diameter), the levels of serum sex hormone (estradiol, progesterone, testosterone), and gonadotropins (luteinizing hormone, follicle-stimulating hormone) as the outcome of four different CO₂ pneumoperitoneum pressures during laparoscopic surgery.

In their study profile (Figure 1), the authors divided their study population into four groups, where group A was operated with the intra-abdominal of 10 mmHg, whereas all other three groups with 11–12 mmHg pressure. However, they report increased pressure in groups C (13–14 mmHg) and D (15–16 mmHg) in the description of their methods. It seems that more traumatic surgical procedures with significantly longer operation time (94.55±11.7 min) and prolonged adhesiolysis manipulations due to a higher rate of intra-operative adhesions (37.5%) were observed in group D when compared to the other groups (A–C). We believe that higher surgical trauma could overrule any CO₂ pneumoperitoneum impact on postsurgical pituitary and ovarian hormonal functions. Long-lasting surgical procedures in the pelvis (group D) might produce a more pronounced acute inflammatory reaction in the peritoneal cavity with cascade activation of signaling pathways and immune response. Subsequently, therefore, increased levels of pituitary hormones as a reaction to this activated higher inflammatory reaction in patients with the acute severe inflammatory reaction. There are well well-known interactions of inflammation with gonadotropins (4) and also the acute immune reaction and pro-inflammatory cytokines with ovarian hormones, especially with estradiol (5). Transitory changes in blood gases and acid-base parameters during CO₂ pneumoperitoneum evaporate simultaneously with decreased pneumoperitoneum pressure (2,3,6) and its impact is less pronounced than the tissue inflammatory reaction after surgical procedures (6,7). We suggest that the design of this study produces misleading results of CO₂ pneumoperitoneum impact on postsurgical pituitary and ovarian function.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was a standard submission to the journal. The article did not undergo external peer review.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/apm-21-1451). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Qin J, Song G, Jiang Y, et al. Low-pressure pneumoperitoneum reduces influence on ovarian hormones in infertile women: a randomised trial. Ann Palliat Med 2021;10:5746-53. [Crossref] [PubMed]
2. Mynbaev OA, Corona R. Possible mechanisms of peritoneal tissue-oxygen tension changes during CO2-pneumoperitoneum: the role of design, methodology and animal models. Hum Reprod 2009;24:1242-6. [Crossref] [PubMed]
3. Mynbaev OA, Molinas CR, Adamyan LV, et al. Pathogenesis of CO(2) pneumoperitoneum-induced metabolic hypoxemia in a rabbit model. J Am Assoc Gynecol Laparosc 2002;9:306-14. [Crossref] [PubMed]
4. Barabás K, Szabó-Meleg E, Ábrahám IM. Effect of Inflammation on Female Gonadotropin-Releasing Hormone (GnRH) Neurons: Mechanisms and Consequences. Int J Mol Sci 2020;21:529. [Crossref] [PubMed]
5. Stubelius A, Andersson A, Islander U, et al. Ovarian hormones in innate inflammation. Immunobiology 2017;222:878-83. [Crossref] [PubMed]
6. Mynbaev OA, Eliseeva MY, Kalzhanov ZR, et al. Surgical trauma and CO2-insufflation impact on adhesion formation in parietal and visceral peritoneal lesions. Int J Clin Exp Med 2013;6:153-65. [PubMed]
7. Pismensky SV, Kalzhanov ZR, Eliseeva MY, et al. Severe inflammatory reaction induced by peritoneal trauma is the key driving mechanism of postoperative adhesion formation. BMC Surg 2011;11:30. [Crossref] [PubMed]