Gene and Germline Editing in Maternal and Reproductive Health:  A Narrative Review of Ethical Dilemmas and Scientific Advances

Donel Suhaimi; Sofyan Andri; Anastasya Hutapea; Sandi Arihta

doi:10.24198/obgynia.v9i1.939

Gene and Germline Editing in Maternal and Reproductive Health: A Narrative Review of Ethical Dilemmas and Scientific Advances

Donel Suhaimi, Sofyan Andri, Anastasya Hutapea, Sandi Arihta

Abstract

Introduction: In Utero Genetic Editing (IUGE) is an emerging technology intended to modify the fetal genome to prevent or treat genetic disorders before birth. While it presents significant medical potential, it raises complex ethical, legal, and regulatory challenges. Current interventions remain largely animal-based, with human applications at theoretical or preclinical stages.
Methods: This review examines ethical guidelines, legal frameworks, and regulatory perspectives globally and in Indonesia. Sources included WHO, the Indonesian Obstetrics and Gynecology Association (POGI), Indonesian health laws, and journals such as the American Journal of Obstetrics and Gynecology (AJOG). Literature was drawn from PubMed, WHO databases, Indonesian archives, and AJOG publications (2015–2025).
Results: WHO emphasized precaution and transparency, while POGI stressed maternal–fetal safety under strict oversight. Indonesia lacks specific regulation, requiring interventions to respect safety and human dignity. The United States and European Union maintain restrictive regulations, including embryo research bans.
Conclusion: IUGE is promising for reproductive health but remains ethically and legally unresolved, requiring clearer frameworks before clinical translation.

Abstrak
Pendahuluan: In Utero Genetic Editing (IUGE) merupakan teknologi baru untuk memodifikasi genom janin guna mencegah atau mengobati kelainan genetik sejak sebelum lahir. Teknologi ini menjanjikan manfaat medis, namun menimbulkan tantangan etik, hukum, dan regulasi. Hingga kini, sebagian besar intervensi masih berbasis penelitian hewan, sementara aplikasi pada manusia berada pada tahap teoritis atau pra-klinis.
Metode: Kajian ini menelaah pedoman etik, kerangka hukum, dan regulasi dari perspektif global dan Indonesia. Sumber mencakup WHO, Perkumpulan Obstetri dan Ginekologi Indonesia (POGI), peraturan kesehatan nasional, serta jurnal internasional seperti American Journal of Obstetrics and Gynecology (AJOG). Literatur diperoleh dari PubMed, basis data WHO, arsip hukum Indonesia, dan publikasi AJOG (2015–2025).
Hasil: WHO menekankan prinsip kehati-hatian dan transparansi, sementara POGI menegaskan keselamatan ibu–janin dengan pengawasan ketat. Indonesia belum memiliki regulasi khusus, tetapi mensyaratkan intervensi genetik menjaga keselamatan dan martabat manusia. Negara seperti Amerika Serikat dan Uni Eropa menetapkan aturan restriktif, termasuk larangan riset embrio.
Kesimpulan: IUGE berpotensi meningkatkan kesehatan reproduksi, namun memerlukan regulasi yang lebih jelas sebelum penerapan klinis.

Kata kunci: In Utero Genetic Editing, etika, regulasi, terapi janin, bioetika

Keywords

In Utero Genetic Editing, ethics, regulation, fetal therapy, bioethics

Full Text:

PDF

References

Huang N, Chi H, Qiao J. Role of Regulatory T Cells in Regulating Fetal-Maternal Immune Tolerance in Healthy Pregnancies and Reproductive Diseases. Vol. 11, Frontiers in Immunology. Frontiers Media S.A.; 2020.

Shanahan MA, Aagaard KM, McCullough LB, Chervenak FA, Shamshirsaz AA. Society for Maternal-Fetal Medicine Special Statement: Beyond the scalpel: in utero fetal gene therapy and curative medicine. Am J Obstet Gynecol [Internet]. 2021;225(6):B9–18. Avail.

Gupta RM, Musunuru K. Expanding the genetic editing tool kit: ZFNs, TALENs, and CRISPR-Cas9. Vol. 124, Journal of Clinical Investigation. American Society for Clinical Investigation; 2014. p. 4154–61.

Bose SK, Kennedy K, Peranteau WH. Foetal genome editing. Vol. 35, Current Opinion in Obstetrics and Gynecology. Lippincott Williams and Wilkins; 2023. p. 134–9.

Ricciardi AS, Bahal R, Farrelly JS, Quijano E, Bianchi AH, Luks VL, et al. In utero nanoparticle delivery for site-specific genome editing. Nat Commun. 2018 Dec 1;9(1).

Mattar CNZ, Chan JKY, Choolani M. Gene modification therapies for hereditary diseases in the fetus. Vol. 43, Prenatal Diagnosis. John Wiley and Sons Ltd; 2023. p. 674–86.

Caplan AL, Wilson JM. The ethical challenges of in utero gene therapy. Nat Genet. 2000;24:107–107.

Peranteau WH, Flake AW. The Future of In Utero Gene Therapy. Mol Diagn Ther. 2020 Apr 1;24(2):135–42.

WHO. HUMAN GENOME EDITING : A FRAMEWORK FOR GOVERNANCE WHO Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing. 2021.

Riley JS, Luks VL, Berkowitz CL, Dumitru AM, Kus NJ, Dave A, et al. Preexisting maternal immunity to AAV but not Cas9 impairs in utero gene editing in mice. Journal of Clinical Investigation. 2024 Jun 17;134(12).

Breckenfelder C, McGrath P, Matsuda J, Bilosouva G, Rozance P, Anthony R, et al. 39 Developing an Approach for In Utero Gene Editing: Lessons Learned. Am J Obstet Gynecol. 2024 Jan;230(1):S30.

Cartier-Lacave N, Ali R, Ylä-Herttuala S, Kato K, Baetschi B, Lovell-Badge R, et al. Debate on Germline Gene Editing. Vol. 27, Human Gene Therapy Methods. Mary Ann Liebert Inc.; 2016. p. 135–42.

POGI. Panduan Etik dan Profesionalisme Obstetri dan Ginekologi di Indonesia. 2017.

UNESCO. Universal Declaration on the Human Genome and Human Rights (1997) and International Declaration on Human Genetic Data (2003). In 2017 [cited 2025 Mar 15]. Available from: https://unesdoc.unesco.org/ark:/48223/pf0000253908.

Barry S Coller. Ethics of human genome editing. Vol. 70, Annual Review of Medicine. Annual Reviews Inc.; 2019. p. 289–305.

Ormond KE, Mortlock DP, Scholes DT, Bombard Y, Brody LC, Faucett WA, et al. Human Germline Genome Editing. Vol. 101, American Journal of Human Genetics. Cell Press; 2017. p. 167–76.

Moitra K, Garcia S, Jaldin M, Etoundi C, Cooper D, Roland A, et al. ABCC6 and pseudoxanthoma elasticum: The face of a rare disease from genetics to advocacy. Vol. 18, International Journal of Molecular Sciences. MDPI AG; 2017.

Daniels N. Breaking Bioethics Special Section: In Pursuit of Perfect People: The Ethics of Enhancement Normal Functioning and the Treatment-Enhancement Distinction. 2000.

Carbine NE, Lostumbo L, Wallace J, Ko H. Risk-reducing mastectomy for the prevention of primary breast cancer. Vol. 2018, Cochrane Database of Systematic Reviews. John Wiley and Sons Ltd; 2018.

Cohen J, Pertsemlidis A, Kotowski IK, Graham R, Garcia CK, Hobbs HH. Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat Genet. 2005 Feb;37(2):161–5.

President Council Bioethics. Beyond Therapy: Biotechnology and the Pursuit of Happiness [Internet]. 2003. Available from: www.bioethics.gov.

Darnovsky M, Hosman E. Acknowledgements About Center for Genetics and Society [Internet]. 2015. Available from: www.geneticsandsociety.org.

Kosicki M, Tomberg K, Bradley A. Repair of double-strand breaks induced by CRISPR–Cas9 leads to large deletions and complex rearrangements. Nat Biotechnol. 2018 Sep 1;36(8):765–71.

Breckenfelder C, McGrath P, Matsuda J, Bilosouva G, Rozance P, Anthony R, et al. 39 Developing an Approach for In Utero Gene Editing: Lessons Learned. Am J Obstet Gynecol. 2024 Jan;230(1):S30.

DOI: http://dx.doi.org/10.24198/obgynia.v9i1.939