Anticentromere antibodies are the most potent antinuclear antibodies in reducing live birth outcomes after ICSI

Shokichi Teramoto; Tsuyoshi Ueno; Fumihito Aono; Tsuyoshi Okubo; Tomoya Segawa; Hisao Osada; Makio Shozu

doi:10.1016/j.rbmo.2024.103864

Anticentromere antibodies are the most potent antinuclear antibodies in reducing live birth outcomes after ICSI

Reprod Biomed Online. 2024 Feb 7;49(1):103864. doi: 10.1016/j.rbmo.2024.103864. Online ahead of print.

Authors

Shokichi Teramoto¹, Tsuyoshi Ueno², Fumihito Aono¹, Tsuyoshi Okubo², Tomoya Segawa³, Hisao Osada¹, Makio Shozu⁴

Affiliations

¹ Natural ART Clinic at Nihonbashi, 2-7-1, Nihonbashi, Chuo-ku, Tokyo, Japan, 103-6008.
² Shimbashi Yume Clinic, 2-5-1, Shimbashi, Minato-ku, Tokyo, Japan, 105-0004.
³ Natural ART Clinic at Nihonbashi, 2-7-1, Nihonbashi, Chuo-ku, Tokyo, Japan, 103-6008.; Shimbashi Yume Clinic, 2-5-1, Shimbashi, Minato-ku, Tokyo, Japan, 105-0004.
⁴ Natural ART Clinic at Nihonbashi, 2-7-1, Nihonbashi, Chuo-ku, Tokyo, Japan, 103-6008.; Evolution and Reproduction Biology, Medical Mycology Research Center, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba, Chiba Prefecture, Japan, 260-8673.. Electronic address: shozumakio@chiba-u.jp.

PMID: 38688121
DOI: 10.1016/j.rbmo.2024.103864

Abstract

Research question: How, and to what extent, do anticentromere antibodies (ACA) reduce live birth outcomes after ICSI?

Study design: Retrospective cohort study of infertile women aged 30-43 years who underwent ICSI between September 2016 and March 2021. Women with a history or current diagnosis of symptomatic connective tissue disease were excluded. Immunofluorescence staining detected antinuclear antibodies (ANA). Staining pattern and titre (cut-off, 1:160) were used to divide infertile women into three groups: positive for ACA (ACA+) (n = 28); positive for ANA other than ACA (ANA+) (n = 77); and negative for both ACA and ANA (control) (n = 3723).

Results: Cumulative live birth rate (CLB) was lowest in ACA+ (7%, 31% and 46% in ACA+, ANA+ and control, respectively) (ACA+ versus control, P < 0.0001; ACA+ versus ANA+, P = 0.011; ANA+ versus control, P = 0.012). A small impairment in meiosis I and a larger impairment in meiosis II, fertilization and embryo cleavage caused the decrease. Multiple pronuclei formation increased (RR versus control, 5.33; 95% CI 4.26 to 6.65) and good-quality blastocyst development decreased (RR 0.34; 95% CI 0.22 to 0.53). Multiple logistic regression analysis showed that ACA was associated with CLB outcome (OR 0.08, 95% CI 0.02 to 0.36); the other four ANA staining patterns were not.

Conclusions: The effect of ACA on live birth outcomes is strongest after ICSI among ANA, primarily through the impairment of meiosis II and subsequent stages. Repeated ICSI failure and eggs with multiple pronuclei may warrant specific testing for ACA.

Keywords: anticentromere antibody; antinuclear antibody; intracytoplasmic sperm injection; multiple pronucleus.