Investigating dosage effects of ovulation inhibitors on oocyte maturation in assisted reproductive technology: A retrospective study among patients with normal ovarian reserve
The judicious selection of ovulation inhibitors in ovarian stimulation protocols is crucial for the success of assisted reproductive technology (ART). Herein, we investigate the dose-dependent effects of chlormadinone acetate (CMA) and cetrorelix, two distinct ovulation inhibitors, on oocyte maturat...
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| Veröffentlicht in: | PloS one 2025-01, Vol.20 (1), p.e0317103 |
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| creator | Handa, Mika Takiuchi, Tsuyoshi Kawaguchi, Sumika Ohara, Yasuhiro Doshida, Masakazu Takeuchi, Takumi Matsubayashi, Hidehiko Ishikawa, Tomomoto Komukai, Sho Kitamura, Tetsuhisa Kimura, Tadashi |
| description | The judicious selection of ovulation inhibitors in ovarian stimulation protocols is crucial for the success of assisted reproductive technology (ART). Herein, we investigate the dose-dependent effects of chlormadinone acetate (CMA) and cetrorelix, two distinct ovulation inhibitors, on oocyte maturation in patients with normal ovarian reserve, using univariable and multivariable Poisson regression analyses. Patients undergoing progestin-primed ovarian stimulation (PPOS) with CMA (n = 299) or gonadotropin-releasing hormone antagonist (GnRH-ant) with cetrorelix (n = 605) during their initial in vitro fertilization cycle were enrolled at our center from March 2018 to October 2020 (N = 904). The primary and secondary outcomes were the oocyte maturation and fertilization rates, respectively. After adjusting for several covariates including age, anti-Müllerian hormone levels, total gonadotropin dose, and type of trigger, we calculated the dose-dependent adjusted relative risk (aRR) and 95% confidence interval (CI) for 1 mg of CMA or 0.25 mg of cetrorelix. In the PPOS group, the median age was 34.0 years, and the median total CMA dosage was 22 mg (interquartile range [IQR]: 18.0-32.0). In the GnRH-ant group, the median age was 35.0 years, and the median total cetrorelix dosage was 0.5 mg (IQR 0.5-0.5). The aRR of the maturation rate was 1.003 (95% CI: 0.999-1.007) with PPOS (p = 0.194) and 1.009 (95% CI: 0.962-1.059) with GnRH-ant (p = 0.717). The aRR of the fertilization rate was 1.002 (95% CI: 0.985-1.020) with PPOS (p = 0.783) and 1.022 (95% CI: 0.839-1.246) with GnRH-ant (p = 0.829). Collectively, these findings indicate that within the applied dosages, ovulation inhibitors do not significantly impact oocyte maturation or fertilization rates in patients with normal ovarian reserve. These valuable insights can be applied when designing ART protocols and may guide clinicians in optimizing infertility treatments. |
| doi_str_mv | 10.1371/journal.pone.0317103 |
| format | Article |
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Herein, we investigate the dose-dependent effects of chlormadinone acetate (CMA) and cetrorelix, two distinct ovulation inhibitors, on oocyte maturation in patients with normal ovarian reserve, using univariable and multivariable Poisson regression analyses. Patients undergoing progestin-primed ovarian stimulation (PPOS) with CMA (n = 299) or gonadotropin-releasing hormone antagonist (GnRH-ant) with cetrorelix (n = 605) during their initial in vitro fertilization cycle were enrolled at our center from March 2018 to October 2020 (N = 904). The primary and secondary outcomes were the oocyte maturation and fertilization rates, respectively. After adjusting for several covariates including age, anti-Müllerian hormone levels, total gonadotropin dose, and type of trigger, we calculated the dose-dependent adjusted relative risk (aRR) and 95% confidence interval (CI) for 1 mg of CMA or 0.25 mg of cetrorelix. In the PPOS group, the median age was 34.0 years, and the median total CMA dosage was 22 mg (interquartile range [IQR]: 18.0-32.0). In the GnRH-ant group, the median age was 35.0 years, and the median total cetrorelix dosage was 0.5 mg (IQR 0.5-0.5). The aRR of the maturation rate was 1.003 (95% CI: 0.999-1.007) with PPOS (p = 0.194) and 1.009 (95% CI: 0.962-1.059) with GnRH-ant (p = 0.717). The aRR of the fertilization rate was 1.002 (95% CI: 0.985-1.020) with PPOS (p = 0.783) and 1.022 (95% CI: 0.839-1.246) with GnRH-ant (p = 0.829). Collectively, these findings indicate that within the applied dosages, ovulation inhibitors do not significantly impact oocyte maturation or fertilization rates in patients with normal ovarian reserve. These valuable insights can be applied when designing ART protocols and may guide clinicians in optimizing infertility treatments.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0317103</identifier><identifier>PMID: 39820188</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acetic acid ; Adult ; Biology and Life Sciences ; Body mass index ; Care and treatment ; Confidence intervals ; Dosage ; Dosage and administration ; Dose-response relationship (Biochemistry) ; Dose-Response Relationship, Drug ; Female ; Fertility drugs ; Fertilization in Vitro - methods ; Gametocytes ; Gonadotropin-releasing hormone ; Gonadotropin-Releasing Hormone - analogs & derivatives ; Gonadotropin-Releasing Hormone - antagonists & inhibitors ; Gonadotropins ; Health aspects ; Hormone Antagonists - administration & dosage ; Hormone Antagonists - pharmacology ; Humans ; In vitro fertilization ; Infertility ; Infertility, Female ; Inhibitors ; Maturation ; Medical treatment ; Medicine and Health Sciences ; Methods ; Oocytes ; Oocytes - drug effects ; Oocytes - growth & development ; Ovarian Reserve - drug effects ; Ovulation ; Ovulation Induction - methods ; Patient outcomes ; Physical Sciences ; Pituitary (anterior) ; Pregnancy ; Progestin ; Regression analysis ; Reproductive Techniques, Assisted ; Reproductive technologies ; Reproductive technology ; Research and Analysis Methods ; Retrospective Studies ; Statistical analysis ; Stimulation</subject><ispartof>PloS one, 2025-01, Vol.20 (1), p.e0317103</ispartof><rights>Copyright: © 2025 Handa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>COPYRIGHT 2025 Public Library of Science</rights><rights>2025 Handa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2025 Handa et al 2025 Handa et al</rights><rights>2025 Handa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c4417-c02a38fe061d245db790dee0ddb977e4b3465518bf6b89dee4a69552e7d4f5ee3</cites><orcidid>0000-0002-6527-434X ; 0000-0002-0605-5219 ; 0000-0002-4329-2520</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737757/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737757/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39820188$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Handa, Mika</creatorcontrib><creatorcontrib>Takiuchi, Tsuyoshi</creatorcontrib><creatorcontrib>Kawaguchi, Sumika</creatorcontrib><creatorcontrib>Ohara, Yasuhiro</creatorcontrib><creatorcontrib>Doshida, Masakazu</creatorcontrib><creatorcontrib>Takeuchi, Takumi</creatorcontrib><creatorcontrib>Matsubayashi, Hidehiko</creatorcontrib><creatorcontrib>Ishikawa, Tomomoto</creatorcontrib><creatorcontrib>Komukai, Sho</creatorcontrib><creatorcontrib>Kitamura, Tetsuhisa</creatorcontrib><creatorcontrib>Kimura, Tadashi</creatorcontrib><title>Investigating dosage effects of ovulation inhibitors on oocyte maturation in assisted reproductive technology: A retrospective study among patients with normal ovarian reserve</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The judicious selection of ovulation inhibitors in ovarian stimulation protocols is crucial for the success of assisted reproductive technology (ART). Herein, we investigate the dose-dependent effects of chlormadinone acetate (CMA) and cetrorelix, two distinct ovulation inhibitors, on oocyte maturation in patients with normal ovarian reserve, using univariable and multivariable Poisson regression analyses. Patients undergoing progestin-primed ovarian stimulation (PPOS) with CMA (n = 299) or gonadotropin-releasing hormone antagonist (GnRH-ant) with cetrorelix (n = 605) during their initial in vitro fertilization cycle were enrolled at our center from March 2018 to October 2020 (N = 904). The primary and secondary outcomes were the oocyte maturation and fertilization rates, respectively. After adjusting for several covariates including age, anti-Müllerian hormone levels, total gonadotropin dose, and type of trigger, we calculated the dose-dependent adjusted relative risk (aRR) and 95% confidence interval (CI) for 1 mg of CMA or 0.25 mg of cetrorelix. In the PPOS group, the median age was 34.0 years, and the median total CMA dosage was 22 mg (interquartile range [IQR]: 18.0-32.0). In the GnRH-ant group, the median age was 35.0 years, and the median total cetrorelix dosage was 0.5 mg (IQR 0.5-0.5). The aRR of the maturation rate was 1.003 (95% CI: 0.999-1.007) with PPOS (p = 0.194) and 1.009 (95% CI: 0.962-1.059) with GnRH-ant (p = 0.717). The aRR of the fertilization rate was 1.002 (95% CI: 0.985-1.020) with PPOS (p = 0.783) and 1.022 (95% CI: 0.839-1.246) with GnRH-ant (p = 0.829). Collectively, these findings indicate that within the applied dosages, ovulation inhibitors do not significantly impact oocyte maturation or fertilization rates in patients with normal ovarian reserve. These valuable insights can be applied when designing ART protocols and may guide clinicians in optimizing infertility treatments.</description><subject>Acetic acid</subject><subject>Adult</subject><subject>Biology and Life Sciences</subject><subject>Body mass index</subject><subject>Care and treatment</subject><subject>Confidence intervals</subject><subject>Dosage</subject><subject>Dosage and administration</subject><subject>Dose-response relationship (Biochemistry)</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Fertility drugs</subject><subject>Fertilization in Vitro - methods</subject><subject>Gametocytes</subject><subject>Gonadotropin-releasing hormone</subject><subject>Gonadotropin-Releasing Hormone - analogs & derivatives</subject><subject>Gonadotropin-Releasing Hormone - antagonists & inhibitors</subject><subject>Gonadotropins</subject><subject>Health aspects</subject><subject>Hormone Antagonists - administration & 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Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Handa, Mika</au><au>Takiuchi, Tsuyoshi</au><au>Kawaguchi, Sumika</au><au>Ohara, Yasuhiro</au><au>Doshida, Masakazu</au><au>Takeuchi, Takumi</au><au>Matsubayashi, Hidehiko</au><au>Ishikawa, Tomomoto</au><au>Komukai, Sho</au><au>Kitamura, Tetsuhisa</au><au>Kimura, Tadashi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Investigating dosage effects of ovulation inhibitors on oocyte maturation in assisted reproductive technology: A retrospective study among patients with normal ovarian reserve</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2025-01-16</date><risdate>2025</risdate><volume>20</volume><issue>1</issue><spage>e0317103</spage><pages>e0317103-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The judicious selection of ovulation inhibitors in ovarian stimulation protocols is crucial for the success of assisted reproductive technology (ART). Herein, we investigate the dose-dependent effects of chlormadinone acetate (CMA) and cetrorelix, two distinct ovulation inhibitors, on oocyte maturation in patients with normal ovarian reserve, using univariable and multivariable Poisson regression analyses. Patients undergoing progestin-primed ovarian stimulation (PPOS) with CMA (n = 299) or gonadotropin-releasing hormone antagonist (GnRH-ant) with cetrorelix (n = 605) during their initial in vitro fertilization cycle were enrolled at our center from March 2018 to October 2020 (N = 904). The primary and secondary outcomes were the oocyte maturation and fertilization rates, respectively. After adjusting for several covariates including age, anti-Müllerian hormone levels, total gonadotropin dose, and type of trigger, we calculated the dose-dependent adjusted relative risk (aRR) and 95% confidence interval (CI) for 1 mg of CMA or 0.25 mg of cetrorelix. In the PPOS group, the median age was 34.0 years, and the median total CMA dosage was 22 mg (interquartile range [IQR]: 18.0-32.0). In the GnRH-ant group, the median age was 35.0 years, and the median total cetrorelix dosage was 0.5 mg (IQR 0.5-0.5). The aRR of the maturation rate was 1.003 (95% CI: 0.999-1.007) with PPOS (p = 0.194) and 1.009 (95% CI: 0.962-1.059) with GnRH-ant (p = 0.717). The aRR of the fertilization rate was 1.002 (95% CI: 0.985-1.020) with PPOS (p = 0.783) and 1.022 (95% CI: 0.839-1.246) with GnRH-ant (p = 0.829). Collectively, these findings indicate that within the applied dosages, ovulation inhibitors do not significantly impact oocyte maturation or fertilization rates in patients with normal ovarian reserve. These valuable insights can be applied when designing ART protocols and may guide clinicians in optimizing infertility treatments.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>39820188</pmid><doi>10.1371/journal.pone.0317103</doi><tpages>e0317103</tpages><orcidid>https://orcid.org/0000-0002-6527-434X</orcidid><orcidid>https://orcid.org/0000-0002-0605-5219</orcidid><orcidid>https://orcid.org/0000-0002-4329-2520</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2025-01, Vol.20 (1), p.e0317103 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_3156421604 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Acetic acid Adult Biology and Life Sciences Body mass index Care and treatment Confidence intervals Dosage Dosage and administration Dose-response relationship (Biochemistry) Dose-Response Relationship, Drug Female Fertility drugs Fertilization in Vitro - methods Gametocytes Gonadotropin-releasing hormone Gonadotropin-Releasing Hormone - analogs & derivatives Gonadotropin-Releasing Hormone - antagonists & inhibitors Gonadotropins Health aspects Hormone Antagonists - administration & dosage Hormone Antagonists - pharmacology Humans In vitro fertilization Infertility Infertility, Female Inhibitors Maturation Medical treatment Medicine and Health Sciences Methods Oocytes Oocytes - drug effects Oocytes - growth & development Ovarian Reserve - drug effects Ovulation Ovulation Induction - methods Patient outcomes Physical Sciences Pituitary (anterior) Pregnancy Progestin Regression analysis Reproductive Techniques, Assisted Reproductive technologies Reproductive technology Research and Analysis Methods Retrospective Studies Statistical analysis Stimulation |
| title | Investigating dosage effects of ovulation inhibitors on oocyte maturation in assisted reproductive technology: A retrospective study among patients with normal ovarian reserve |
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