Preimplantation genetic testing for aneuploidy in severe male factor infertility: protocol for a multicenter randomised controlled trial

Xian-Hua Lin, Meng-Xi Guo, Dan-Dan Wu, Yao Lu, Jian-Lin Zhang, Cheng-Liang Zhou, Li Jin, Li Wang, Chen Zhang, Chen-Ming Xu, Song-Chang Chen, Song-Ying Zhang, Xiao-Xi Sun, Yan-Ting Wu, Yun Sun, He-Feng Huang, Xian-Hua Lin, Meng-Xi Guo, Dan-Dan Wu, Yao Lu, Jian-Lin Zhang, Cheng-Liang Zhou, Li Jin, Li Wang, Chen Zhang, Chen-Ming Xu, Song-Chang Chen, Song-Ying Zhang, Xiao-Xi Sun, Yan-Ting Wu, Yun Sun, He-Feng Huang

Abstract

Introduction: Conventional intracytoplasmic sperm injection (ICSI) is a widely used treatment for couples with severe male infertility. However, there are controversies regarding the selection and the damage to gametes during the ICSI procedure. Although preimplantation genetic testing for aneuploidies (PGT-A) can give genetic information about embryos for transfer and improve fertility rate, and it is widely used in women with recurrent spontaneous abortion or advanced age, PGT-A is not only more expensive but also has unclear effectiveness with respect to the improvement of fertility rate among couples with severe male infertility. High-quality, well-powered randomised clinical trials (RCTs) comparing ICSI+PGT-A and ICSI are lacking.

Methods and analysis: This is a protocol for a multicenter, open-label RCT in four reproductive medical centers qualified for PGT technique in China. We will study couples with severe male infertility scheduled for their fertility treatment. After the blastocyst culture, eligible participants are randomised to the ICSI+PGT-A group or the conventional ICSI group in a 1:1 ratio. Other assisted reproductive procedures are similar and parallel between the two groups. The primary outcome will be live birth rate and cumulative live-birth rate . Secondary outcomes will be embryo implantation rate, biochemical pregnancy rate, clinical pregnancy rate, spontaneous abortion rate, ongoing pregnancy rate, preterm birth rate, fetal chromosomal abnormality rate, birth defect rate and treatment complications. To demonstrate or refute a difference between the two groups, we plan to include 188 participants in each group; taking consideration of 20% of dropout, the total target sample size is 450.

Ethics and dissemination: Ethical approval was obtained from International Peace Maternity and Child Health Hospital of Shanghai Jiao Tong University Medical Science Research Ethics Committee (GKLW2016-16). Informed consent will be obtained from each participant. The findings will be disseminated to the public through conference presentations and publication in peer-reviewed scientific journals.

Trial registration number: ClinicalTrials.gov, NCT02941965.

Keywords: genetics; male infertility; protocols & guidelines; reproductive medicine.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Flowchart for enrollment, allocation, treatment and follow-up of study participants. ICSI, intracytoplasmic sperm injection; PGT-A, preimplantation genetic testing for aneuploidies.

References

    1. Bhasin S, de Kretser DM, Baker HW. Clinical review 64: pathophysiology and natural history of male infertility. J Clin Endocrinol Metab 1994;79:1525–9. 10.1210/jcem.79.6.7989450
    1. Agarwal A, Mulgund A, Hamada A, et al. . A unique view on male infertility around the globe. Reprod Biol Endocrinol 2015;13:37. 10.1186/s12958-015-0032-1
    1. Palermo G, Joris H, Devroey P, et al. . Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet 1992;340:17–18. 10.1016/0140-6736(92)92425-F
    1. Xu R, Ding Y, Wang Y, et al. . Comparison of preimplantation genetic testing for aneuploidy versus intracytoplasmic sperm injection in severe male infertility. Andrologia 2021;53:e14065. 10.1111/and.14065
    1. Boulet SL, Mehta A, Kissin DM, et al. . Trends in use of and reproductive outcomes associated with intracytoplasmic sperm injection. JAMA 2015;313:255–63. 10.1001/jama.2014.17985
    1. Inhorn MC, Patrizio P. Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century. Hum Reprod Update 2015;21:411–26. 10.1093/humupd/dmv016
    1. Bonduelle M, Wennerholm U-B, Loft A, et al. . A multi-centre cohort study of the physical health of 5-year-old children conceived after intracytoplasmic sperm injection, in vitro fertilization and natural conception. Hum Reprod 2005;20:413–9. 10.1093/humrep/deh592
    1. Lathi RB, Milki AA. Rate of aneuploidy in miscarriages following in vitro fertilization and intracytoplasmic sperm injection. Fertil Steril 2004;81:1270–2. 10.1016/j.fertnstert.2003.09.065
    1. Coates A, Hesla JS, Hurliman A, et al. . Use of suboptimal sperm increases the risk of aneuploidy of the sex chromosomes in preimplantation blastocyst embryos. Fertil Steril 2015;104:866–72. 10.1016/j.fertnstert.2015.06.033
    1. Jungwirth A, Giwercman A, Tournaye H, et al. . European association of urology guidelines on male infertility: the 2012 update. Eur Urol 2012;62:324–32. 10.1016/j.eururo.2012.04.048
    1. Esteves SC, Roque M, Bedoschi G, et al. . Intracytoplasmic sperm injection for male infertility and consequences for offspring. Nat Rev Urol 2018;15:535–62. 10.1038/s41585-018-0051-8
    1. In't Veld P, Brandenburg H, Verhoeff A, et al. . Sex chromosomal abnormalities and intracytoplasmic sperm injection. Lancet 1995;346:773. 10.1016/S0140-6736(95)91531-1
    1. Homer HA. Preimplantation genetic testing for aneuploidy (PGT-A): the biology, the technology and the clinical outcomes. Aust N Z J Obstet Gynaecol 2019;59:317–24. 10.1111/ajo.12960
    1. Hodes-Wertz B, Grifo J, Ghadir S, et al. . Idiopathic recurrent miscarriage is caused mostly by aneuploid embryos. Fertil Steril 2012;98:675–80. 10.1016/j.fertnstert.2012.05.025
    1. Yang Z, Liu J, Collins GS, et al. . Selection of single blastocysts for fresh transfer via standard morphology assessment alone and with array CGH for good prognosis IVF patients: results from a randomized pilot study. Mol Cytogenet 2012;5:24. 10.1186/1755-8166-5-24
    1. Keltz MD, Vega M, Sirota I, et al. . Preimplantation genetic screening (PGs) with comparative genomic hybridization (CGH) following day 3 single cell blastomere biopsy markedly improves IVF outcomes while lowering multiple pregnancies and miscarriages. J Assist Reprod Genet 2013;30:1333–9. 10.1007/s10815-013-0070-6
    1. Chen M, Wei S, Hu J, et al. . Can comprehensive chromosome screening technology improve IVF/ICSI outcomes? A meta-analysis. PLoS One 2015;10:e0140779. 10.1371/journal.pone.0140779
    1. Levron J, Aviram-Goldring A, Madgar I, et al. . Sperm chromosome abnormalities in men with severe male factor infertility who are undergoing in vitro fertilization with intracytoplasmic sperm injection. Fertil Steril 2001;76:479–84. 10.1016/S0015-0282(01)01957-4
    1. Harper J, Coonen E, De Rycke M, et al. . What next for preimplantation genetic screening (PGs)? A position statement from the ESHRE Pgd Consortium Steering Committee. Hum Reprod 2010;25:821–3. 10.1093/humrep/dep476
    1. Menkveld R. Clinical significance of the low normal sperm morphology value as proposed in the fifth edition of the who laboratory manual for the examination and processing of human semen. Asian J Androl 2010;12:47–58. 10.1038/aja.2009.14
    1. Oehninger S, Veeck L, Lanzendorf S, et al. . Intracytoplasmic sperm injection: achievement of high pregnancy rates in couples with severe male factor infertility is dependent primarily upon female and not male factors. Fertil Steril 1995;64:977–81. 10.1016/S0015-0282(16)57913-8
    1. Desai NN, Goldstein J, Rowland DY, et al. . Morphological evaluation of human embryos and derivation of an embryo quality scoring system specific for day 3 embryos: a preliminary study. Hum Reprod 2000;15:2190–6. 10.1093/humrep/15.10.2190
    1. Kondo I, Suganuma N, Ando T, et al. . Clinical factors for successful cryopreserved-thawed embryo transfer. J Assist Reprod Genet 1996;13:201–6. 10.1007/BF02065936
    1. Gardner DK, Lane M, Stevens J, et al. . Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. Fertil Steril 2000;73:1155–8. 10.1016/S0015-0282(00)00518-5

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