Reproductive biomedicine online · 2026
Haematopoietic loss of the X chromosome is associated with a lower likelihood of natural conception.
СтатьяМногоцентровое исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Kikuchi Taiki, Yoshida Naofumi, Yoneyama Shintaro, Maki Yoshinori, Kitada Kohei, Hamuro Akihiro, Misugi Takuya, Kubo Tomohiro, Nakamura Yoshihiro, Haruki Atsushi, Tachibana Daisuke, Sano Soichi
Аннотация
RESEARCH QUESTION: Is haematopoietic loss of the X chromosome (LOX), which increases with age in women, but whose reproductive relevance is unclear, associated with the likelihood of natural conception?
DESIGN: Multicentre case-control study at three hospitals in Osaka, Japan. Cases were women who did not achieve natural conception after exclusion of male-factor infertility (n = 381). Controls were women who conceived naturally (n = 123). The LOX burden in peripheral blood (%LOX) was quantified by multiplex single-cell droplet digital polymerase chain reaction. Serum anti-Müllerian hormone (AMH) was measured by standardized chemiluminescent enzyme assays. The primary outcome was the difference in %LOX between cases and controls. Secondary analyses assessed assisted reproductive technology (ART) outcomes (pregnancy within three embryo-transfer cycles) among a prospectively followed subset. Exploratory analyses examined correlations of %LOX with age and AMH.
RESULTS: %LOX increased with age (P < 0.001) and was higher in cases than controls (P < 0.001). This difference remained significant after adjusting for age, body mass index (BMI) and prior pregnancy (β = 0.82, 95% CI 0.70 to 0.96, P = 0.013). Receiver operating characteristic curve analysis identified an optimal %LOX threshold of 0.87% (area under the curve 0.60, 95% CI 0.54 to 0.66). Women with %LOX 0.87% or above had over twofold higher odds of not achieving natural conception (OR 2.16, 95% CI 1.40 to 3.32, P < 0.001; age-stratified, BMI-adjusted). In contrast, %LOX was not associated with pregnancy within three ART cycles (adjusted P = 0.23) and did not correlate with AMH (ρ = ‒0.06; P = 0.25) or FSH (ρ = ‒0.01; P = 0.84) levels.
CONCLUSIONS: Haematopoietic LOX was associated with a lower likelihood of natural conception, whereas no clear association was found with ART outcomes was observed.
DESIGN: Multicentre case-control study at three hospitals in Osaka, Japan. Cases were women who did not achieve natural conception after exclusion of male-factor infertility (n = 381). Controls were women who conceived naturally (n = 123). The LOX burden in peripheral blood (%LOX) was quantified by multiplex single-cell droplet digital polymerase chain reaction. Serum anti-Müllerian hormone (AMH) was measured by standardized chemiluminescent enzyme assays. The primary outcome was the difference in %LOX between cases and controls. Secondary analyses assessed assisted reproductive technology (ART) outcomes (pregnancy within three embryo-transfer cycles) among a prospectively followed subset. Exploratory analyses examined correlations of %LOX with age and AMH.
RESULTS: %LOX increased with age (P < 0.001) and was higher in cases than controls (P < 0.001). This difference remained significant after adjusting for age, body mass index (BMI) and prior pregnancy (β = 0.82, 95% CI 0.70 to 0.96, P = 0.013). Receiver operating characteristic curve analysis identified an optimal %LOX threshold of 0.87% (area under the curve 0.60, 95% CI 0.54 to 0.66). Women with %LOX 0.87% or above had over twofold higher odds of not achieving natural conception (OR 2.16, 95% CI 1.40 to 3.32, P < 0.001; age-stratified, BMI-adjusted). In contrast, %LOX was not associated with pregnancy within three ART cycles (adjusted P = 0.23) and did not correlate with AMH (ρ = ‒0.06; P = 0.25) or FSH (ρ = ‒0.01; P = 0.84) levels.
CONCLUSIONS: Haematopoietic LOX was associated with a lower likelihood of natural conception, whereas no clear association was found with ART outcomes was observed.