JBRA Assist. Reprod. 2022;26(04):567-567
EDITORIAL

doi: 10.5935/1518-0557.20220054

MSOME/IMSI versus epigenetic marks: doubts in the past for hopes in the future

Jose Gonçalves Franco Jr1,2,3, Joao Batista A Oliveira1,2

1Center for Human Reproduction Prof. Franco Junior, Ribeirão Preto/SP - Brazil
2Paulista Center for Diagnosis Research and Training, Ribeirão Preto/SP - Brazil
3Editorial Consultant - JBRA Assisted Reproduction

Keywords: MSOME, IMSI, epigenetic marks, sperm vacuoles.

Since 2008, our group has published studies showing a relationship between spermatozoa with vacuoles and increased DNA fragmentation (Franco Jr et al., 2008; Oliveira et al., 2010); as well as an association between sperm with vacuoles and abnormal chromatin packing (Franco Jr et al., 2012). Based on these studies and those of other authors (Garolla et al., 2008), we decided to consider spermatozoa with vacuoles (especially those occupying ≥ 50% nuclear area) as a risk cell for transporting DNA damage, and we started to use selection at high magnification (MSOME/IMSI) as a routine for ICSI cases. During these almost 15 years we have been heavily criticized for this approach based only on basic studies, especially considering the divergence in the literature regarding its efficiency versus ICSI in improving parameters traditionally used in the evaluation of any methodology in assisted reproduction (fertilization rates, clinical pregnancy, live births, etc.). In other words, we would be intensively cultivating one more of these countless adds-on.

In 2021, Dieamant et al. published a systematic review and meta-analysis based on the birth of 3907 children born after IMSI (n=1280) and through ICSI (n=2627). The results demonstrated that IMSI decreased the incidence of structural defects compared to ICSI (p=0.04). However, there was no significant difference in chromosomal abnormalities (Trisomy 13;18; 21 and triple X) between children conceived after IMSI or ICSI. In principle, these data confirm that MSOME/IMSI should not be abandoned, because the identification of birth defects is not something that can be neglected. In principle, assisted reproduction methodologies should not be evaluated only by traditional outcomes, but also by how they would influence the incidence of congenital malformations. This is perhaps the minimum, but in the future epigenetic manifestations could not be ruled out. Could preventing diseases such as obesity, arterial hypertension, diabetes guide scientific thinking in choosing an assisted reproduction methodology? It would be coherent, however with regards to MSOME/IMSI there was a missing link in this scientific thinking. Bendayan et al. (2022) demonstrated that sperm with vacuoles carry altered epigenetic marks (H3K4me3, H3K27me3) compared to sperm without vacuoles. Finally, something that unites all these facts and awakens the need for a change in the judgment of an assisted reproduction methodology. Epigenetic prevention could be a new outcome.

Following this line of thought, MSOME/IMSI could be the first tool in assisted reproduction capable of reducing the risk of transmission of epigenetic problems through spermatozoa. Hallelujah, 15 years of employing MSOME/IMSI may have been worth it!

REFERENCES
Bendayan M, Caceres L, Saïs E, Swierkowski-Blanchard N, Alter L, Bonnet-Garnier A, Boitrelle F. Human Sperm Morphology as a Marker of Its Nuclear Quality and Epigenetic Pattern. Cells. 2022; 11: 1788. PMID: 35681482 DOI: 10.3390/cells11111788. Medline

Dieamant F, Petersen CG, Vagnini LD, Renzi A, Petersen B, Massaro F, Zamara C, Nicoletti A, Ricci J, Oliani AH, Oliveira JBA, Franco JG Jr. Impact of Intracytoplasmic Morphologically Selected Sperm Injection (IMSI) on Birth Defects: A Systematic Review and Meta-Analysis. JBRA Assist Reprod. 2021;25:466-472. PMID: 34224237 DOI: 10.5935/1518-0557.20210030 Medline

Franco JG Jr, Baruffi RL, Mauri AL, Petersen CG, Oliveira JB, Vagnini L. Significance of large nuclear vacuoles in human spermatozoa: implications for ICSI. Reprod Biomed Online. 2008;17:42-5. PMID: 18616888 DOI: 10.1016/s1472-6483(10)60291-x Medline

Franco JG Jr, Mauri AL, Petersen CG, Massaro FC, Silva LF, Felipe V, Cavagna M, Pontes A, Baruffi RL, Oliveira JB, Vagnini LD. Large nuclear vacuoles are indicative of abnormal chromatin packaging in human spermatozoa. Int J Androl. 2012;35:46-51. PMID: 21535011 DOI: 10.1111/j.1365-2605.2011.01154.x Medline

Garolla A, Fortini D, Menegazzo M, De Toni L, Nicoletti V, Moretti A, Selice R, Engl B, Foresta C. High-power microscopy for selecting spermatozoa for ICSI by physiological status. Reprod Biomed Online. 2008;17:610-6. PMID: 18983744. DOI: 10.1016/s1472-6483(10)60307-0. Medline

Oliveira JB, Massaro FC, Baruffi RL, Mauri AL, Petersen CG, Silva LF, Vagnini LD, Franco JG Jr. Correlation between semen analysis by motile sperm organelle morphology examination and sperm DNA damage. Fertil Steril. 2010; 94:1937-40. PMID: 20189558 DOI: 10.1016/j.fertnstert.2010.01.042. Medline