Adverse effects of progestin-primed ovarian stimulation: combination of clinical study and single-cell analysis

Handa, Mika; Takiuchi, Tsuyoshi; Kawaguchi, Sumika; Hon, Chung Chau; Moody, Jonathan; Okazaki, Yasushi; Ozaki, Kokoro; Horie, Masafumi; Ohara, Yasuhiro; Doshida, Masakazu; Takeuchi, Takumi; Matsubayashi, Hidehiko; Saji, Fumie; Miyake, Tatsuya; Ishikawa, Tomomoto; Ando, Yoshinari; Komukai, Sho; Kitamura, Tetsuhisa; Shin, Jay W.; Kimura, Tadashi

doi:https://doi.org/10.1016/j.rbmo.2025.104833

Adverse effects of progestin-primed ovarian stimulation: combination of clinical study and single-cell analysis

Handa, Mika; Takiuchi, Tsuyoshi; Kawaguchi, Sumika et al.

Reproductive BioMedicine Online, 2025, 51(2), 104833

アクセス数:35件（2025-10-19 06:43 集計）

固定URL: https://hdl.handle.net/11094/102651

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タイトル	Adverse effects of progestin-primed ovarian stimulation: combination of clinical study and single-cell analysis
著者	researchmap permalink mikahanda mikahanda 著者名 Handa, Mika
	NRID 1000040733358 1000040733358 researchmap permalink Takiuchi-gyne Takiuchi-gyne Scopus Author ID 51764431400 51764431400 著者名 Takiuchi, Tsuyoshi
	著者名 Kawaguchi, Sumika
	NRID 1000020775671 1000020775671 著者名 Hon, Chung Chau
	著者名 Moody, Jonathan
	NRID 1000080280733 1000080280733 著者名 Okazaki, Yasushi
	NRID 1000010754765 1000010754765 著者名 Ozaki, Kokoro
	著者名 Horie, Masafumi
	著者名 Ohara, Yasuhiro
	著者名 Doshida, Masakazu
	著者名 Takeuchi, Takumi
	著者名 Matsubayashi, Hidehiko
	NRID 1000040600987 1000040600987 researchmap permalink fumi_s fumi_s Scopus Author ID 59768704100 59768704100 著者名 Saji, Fumie
	NRID 1000000814766 1000000814766 researchmap permalink a-1 a-1 Scopus Author ID 57188931396 57188931396 著者名 Miyake, Tatsuya
	NRID 1000000432576 1000000432576 著者名 Ishikawa, Tomomoto
	著者名 Ando, Yoshinari
	NRID 1000070794543 1000070794543 ORCID 0000-0002-4329-2520 0000-0002-4329-2520 researchmap permalink sho.komukai sho.komukai Scopus Author ID 57200127087 57200127087 著者名 Komukai, Sho
	NRID 1000030639810 1000030639810 ORCID 0000-0003-0107-0580 0000-0003-0107-0580 researchmap permalink Kitamura_T Kitamura_T Scopus Author ID 22234282700 22234282700 著者名 Kitamura, Tetsuhisa
	著者名 Shin, Jay W.
	NRID 1000090240845 1000090240845 著者名 Kimura, Tadashi
キーワード等	Inverse probability weighting
	Mitochondrial DNA
	Mural granulosa cell
	Progestin-primed ovarian stimulation
	Single-cell RNA sequencing
内容	Handa M., Takiuchi T., Kawaguchi S., et al. Adverse effects of progestin-primed ovarian stimulation: combination of clinical study and single-cell analysis. Reproductive BioMedicine Online 51, 104833 (2025); https://doi.org/10.1016/j.rbmo.2025.104833.
抄録	Research question: Does progestin-primed ovarian stimulation (PPOS) have a negative effect on reproductive outcomes compared with a gonadotrophin-releasing hormone (GnRH) antagonist protocol? Design: This retrospective cohort study included 907 patients aged <40 years with normal ovarian reserves undergoing either PPOS (n = 299) or a GnRH-antagonist protocol (n = 608) in their first IVF cycle between 2018 and 2020. An additional genetic analysis, single-cell RNA sequencing (scRNA-seq), was performed on the mural granulosa cells (mGC) of metaphase II oocyte follicles retrieved from 16 patients, with the above inclusion criteria, undergoing PPOS (n = 8) or a GnRH-antagonist protocol (n = 8) between 2021 and 2022. Inverse probability of treatment weighting (IPTW) was performed on the clinical data. Predetermined primary outcomes were the premature LH surge rate and the live birth rate of the first frozen embryo transfer cycle for the first and second IPTW analyses, respectively. Results: The premature LH surge rate was lower in the PPOS group compared with the GnRH-antagonist group (3.1% versus 20.1%, OR 0.13, 95% CI 0.07–0.23; P < 0.001) in the first IPTW analysis. The good-quality cleavage embryo rate was lower in the PPOS group compared with the GnRH-antagonist group (37.2% versus 49.1%; P < 0.001). The live birth rate was lower in the PPOS group compared with the GnRH-antagonist group (31.5% versus 42.3%, OR 0.63, 95% CI 0.46–0.86; P = 0.004) in the second IPTW analysis. The scRNA-seq analysis demonstrated higher expression of 12 mitochondrial DNA (mtDNA) genes in the PPOS group compared with the GnRH-antagonist group. Conclusion: PPOS suppressed the premature LH surge rate but was associated with a lower live birth rate compared with the GnRH-antagonist protocol. The elevated expression of mtDNA genes in mGC may also indicate a decline in oocyte quality with PPOS.
出版者	Elsevier Ltd
収録物名	Reproductive BioMedicine Online
巻(号)	51(2)
ページ	104833
刊行年月	2025-07-24
言語	英語
ハンドルURL	https://hdl.handle.net/11094/102651
PISSN	14726483
eISSN	14726491
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1016/j.rbmo.2025.104833
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Reproductive BioMedicine Online. 2025, 51(2), p. 104833
DC.title	Adverse effects of progestin-primed ovarian stimulation: combination of clinical study and single-cell analysis
DC.creator	Handa, Mika
	Takiuchi, Tsuyoshi
	Kawaguchi, Sumika
	Hon, Chung Chau
	Moody, Jonathan
	Okazaki, Yasushi
	Ozaki, Kokoro
	Horie, Masafumi
	Ohara, Yasuhiro
	Doshida, Masakazu
	Takeuchi, Takumi
	Matsubayashi, Hidehiko
	Saji, Fumie
	Miyake, Tatsuya
	Ishikawa, Tomomoto
	Ando, Yoshinari
	Komukai, Sho
	Kitamura, Tetsuhisa
	Shin, Jay W.
	Kimura, Tadashi
DC.publisher	Elsevier Ltd
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-07-24
DC.identifier	https://doi.org/10.1016/j.rbmo.2025.104833
DC.subject	Inverse probability weighting
	Mitochondrial DNA
	Mural granulosa cell
	Progestin-primed ovarian stimulation
	Single-cell RNA sequencing
DC.description	Handa M., Takiuchi T., Kawaguchi S., et al. Adverse effects of progestin-primed ovarian stimulation: combination of clinical study and single-cell analysis. Reproductive BioMedicine Online 51, 104833 (2025); https://doi.org/10.1016/j.rbmo.2025.104833.
DCTERMS.abstract	Research question: Does progestin-primed ovarian stimulation (PPOS) have a negative effect on reproductive outcomes compared with a gonadotrophin-releasing hormone (GnRH) antagonist protocol? Design: This retrospective cohort study included 907 patients aged <40 years with normal ovarian reserves undergoing either PPOS (n = 299) or a GnRH-antagonist protocol (n = 608) in their first IVF cycle between 2018 and 2020. An additional genetic analysis, single-cell RNA sequencing (scRNA-seq), was performed on the mural granulosa cells (mGC) of metaphase II oocyte follicles retrieved from 16 patients, with the above inclusion criteria, undergoing PPOS (n = 8) or a GnRH-antagonist protocol (n = 8) between 2021 and 2022. Inverse probability of treatment weighting (IPTW) was performed on the clinical data. Predetermined primary outcomes were the premature LH surge rate and the live birth rate of the first frozen embryo transfer cycle for the first and second IPTW analyses, respectively. Results: The premature LH surge rate was lower in the PPOS group compared with the GnRH-antagonist group (3.1% versus 20.1%, OR 0.13, 95% CI 0.07–0.23; P < 0.001) in the first IPTW analysis. The good-quality cleavage embryo rate was lower in the PPOS group compared with the GnRH-antagonist group (37.2% versus 49.1%; P < 0.001). The live birth rate was lower in the PPOS group compared with the GnRH-antagonist group (31.5% versus 42.3%, OR 0.63, 95% CI 0.46–0.86; P = 0.004) in the second IPTW analysis. The scRNA-seq analysis demonstrated higher expression of 12 mitochondrial DNA (mtDNA) genes in the PPOS group compared with the GnRH-antagonist group. Conclusion: PPOS suppressed the premature LH surge rate but was associated with a lower live birth rate compared with the GnRH-antagonist protocol. The elevated expression of mtDNA genes in mGC may also indicate a decline in oocyte quality with PPOS.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	102651
citation_title	Adverse effects of progestin-primed ovarian stimulation: combination of clinical study and single-cell analysis
citation_author	Handa, Mika
	Takiuchi, Tsuyoshi
	Kawaguchi, Sumika
	Hon, Chung Chau
	Moody, Jonathan
	Okazaki, Yasushi
	Ozaki, Kokoro
	Horie, Masafumi
	Ohara, Yasuhiro
	Doshida, Masakazu
	Takeuchi, Takumi
	Matsubayashi, Hidehiko
	Saji, Fumie
	Miyake, Tatsuya
	Ishikawa, Tomomoto
	Ando, Yoshinari
	Komukai, Sho
	Kitamura, Tetsuhisa
	Shin, Jay W.
	Kimura, Tadashi
citation_publisher	Elsevier Ltd
citation_language	英語
citation_date	2025-07-24
citation_journal_title	Reproductive BioMedicine Online
citation_volume	51
citation_issue	2
citation_firstpage	104833
citation_doi	https://doi.org/10.1016/j.rbmo.2025.104833
citation_public_url	https://hdl.handle.net/11094/102651

Adverse effects of progestin-primed ovarian stimulation: combination of clinical study and single-cell analysis

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