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The goal of this prospective, observational study is to learn about the pathogenesis and biological target of the subtypes of poor ovarian response (POR) during In vitro fertilization and embryo transfer (IVF-ET). The main question it aims to answer is:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Normal prognosis group (control group) | Participants included in this group should have normal ovarian reserve: number of antral follicle count ≥5, level of anti-Mullerian hormone ≥1.2 ng/ml, and number of oocytes retrieved in the present IVF-ET cycles>9. All participants in this group receive the standard operation protocol for In vitro fertilization and embryo transfer. |
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| Unexpected poor prognosis group | Participants included in this group should have normal ovarian reserve but a poor ovarian response, defined as: number of antral follicle count ≥5, level of anti-Müllerian hormone ≥1.2ng/ml, and number of oocytes retrieved in the present IVF-ET cycles ≤ 9. All participants in this group will receive the standard operation for in vitro fertilization and embryo transfer. |
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| Poor prognosis of advanced maternal age group | Participants included in this group are characterized by advanced age (≥35 years) and meet at least one of the following criteria: 1. Number of oocytes retrieved in the current IVF cycle ≤9; 2. Diminished ovarian reserve: level of anti-Mullerian hormone<1.2 ng/ml or number of antral follicle count <5. All participants in this group receive the standard operation protocol for In vitro fertilization and embryo transfer. |
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| Expected poor prognosis group | Participants included in this group should have diminished ovarian reserve: number of antral follicle count<5 and level of anti-Mullerian hormone<1.2 ng/ml. All participants in this group receive the standard operation protocol for In vitro fertilization and embryo transfer. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Not applicable- observational study | Other | Not applicable- observational study |
|
| Measure | Description | Time Frame |
|---|---|---|
| The relative expression level of SIRT3 mRNA of granulosa cells | The real-time quantitative PCR methods were used to test the relative expression level of SIRT3 mRNA of granulosa cells of each participant among groups. | Detected within three days after oocyte retrieval |
| Measure | Description | Time Frame |
|---|---|---|
| Positive pregnancy rate | Serum β-hCG level ≥ 10mIU/mL, 14 days after embryo transfer. [Detected via ELISA] | 2 weeks after the day of embryo transfer |
| Embryo implantation rate | The number of intrauterine gestational sacs observed divided by the number of embryos transferred. [Detected via ultrasound] |
| Measure | Description | Time Frame |
|---|---|---|
| Levels of follicular fluid metabolites | Patients will be randomly selected from each group and the levels of metabolites (including lactate, pyruvate, malondialdehyde, glutathione) in the follicular fluid will be measured using the corresponding kits. | Detected within three days after oocyte retrieval |
Inclusion Criteria:
Exclusion Criteria:
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The study cohort will prospectively enroll women undergoing in vitro fertilization and embryo transfer (IVF-ET) treatment at the Department of Reproduction and Genetics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, from October 2024 to January 2025. This cohort will be stratified into four study groups based on the following criteria in equal proportions. All participants will receive the standard operation protocol for In vitro fertilization and embryo transfer.
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| Name | Affiliation | Role |
|---|---|---|
| Zhen-Gao Sun, M.D | Affiliated Hospital of Shandong University of Traditional Chinese Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Affiliated Hospital of Shandong University of Traditional Chinese Medicine | Jinan | Shandong | 250011 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31302001 | Background | Wang T, Cao Y, Zheng Q, Tu J, Zhou W, He J, Zhong J, Chen Y, Wang J, Cai R, Zuo Y, Wei B, Fan Q, Yang J, Wu Y, Yi J, Li D, Liu M, Wang C, Zhou A, Li Y, Wu X, Yang W, Chin YE, Chen G, Cheng J. SENP1-Sirt3 Signaling Controls Mitochondrial Protein Acetylation and Metabolism. Mol Cell. 2019 Aug 22;75(4):823-834.e5. doi: 10.1016/j.molcel.2019.06.008. Epub 2019 Jul 10. | |
| 18162286 |
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Follicular fluid from each participant will be collected on the day of egg retrieval under ultrasound guidance (the fluid is usually discarded in routine clinical practice). Granulosa cells will be separated by centrifugation. All of these biospecimen will be stored at -80°C in the Specimen Bank of the Reproductive and Genetic Department at the Affiliatied Hospital of Shandong University of Traditional Chinese Medicine for future analysis. qRT-PCR will be used to examine the relative expression of SIRT3 in granulosa cells. Specialised kits will be used to detect metabolite levels within the follicular fluid.
|
| 3 weeks after the day of embryo transfer |
| Clinical pregnancy rate | An intrauterine gestational sac with fetal heartbeat detected by transvaginal ultrasonography. [Detected via ultrasound] | 4 weeks after the day of embryo transfer |
| Number of oocytes retrieved | The total number of oocytes retrieved in the In Vitro Fertilization and Embryo transfer cycle. | Within 1 day after the oocyte retrieval |
| Average daily dose of gonadotropin per COS cycle | Average daily dose of gonadotropin per COS cycle | Through the process of controlled ovarian stimulation, an average of 10 days |
| Total dosage of gonadotropin per COS cycle | Total dosage of gonadotropin per COS cycle | Through the process of controlled ovarian stimulation, an average of 10 days |
| Gershon E, Plaks V, Dekel N. Gap junctions in the ovary: expression, localization and function. Mol Cell Endocrinol. 2008 Jan 30;282(1-2):18-25. doi: 10.1016/j.mce.2007.11.001. Epub 2007 Nov 19. |
| 33675030 | Background | Imanaka S, Shigetomi H, Kobayashi H. Reprogramming of glucose metabolism of cumulus cells and oocytes and its therapeutic significance. Reprod Sci. 2022 Mar;29(3):653-667. doi: 10.1007/s43032-021-00505-6. Epub 2021 Mar 5. |
| 33020823 | Background | Richani D, Dunning KR, Thompson JG, Gilchrist RB. Metabolic co-dependence of the oocyte and cumulus cells: essential role in determining oocyte developmental competence. Hum Reprod Update. 2021 Jan 4;27(1):27-47. doi: 10.1093/humupd/dmaa043. |
| 15271471 | Background | Gilchrist RB, Ritter LJ, Armstrong DT. Oocyte-somatic cell interactions during follicle development in mammals. Anim Reprod Sci. 2004 Jul;82-83:431-46. doi: 10.1016/j.anireprosci.2004.05.017. |
| 26921622 | Background | Poseidon Group (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number); Alviggi C, Andersen CY, Buehler K, Conforti A, De Placido G, Esteves SC, Fischer R, Galliano D, Polyzos NP, Sunkara SK, Ubaldi FM, Humaidan P. A new more detailed stratification of low responders to ovarian stimulation: from a poor ovarian response to a low prognosis concept. Fertil Steril. 2016 Jun;105(6):1452-3. doi: 10.1016/j.fertnstert.2016.02.005. Epub 2016 Feb 26. No abstract available. |
| 18989307 | Background | Matzuk MM, Lamb DJ. The biology of infertility: research advances and clinical challenges. Nat Med. 2008 Nov;14(11):1197-213. doi: 10.1038/nm.f.1895. Epub 2008 Nov 6. |
| 35451009 | Result | Cozzolino M, Herraiz S, Titus S, Roberts L, Romeu M, Peinado I, Scott RT, Pellicer A, Seli E. Transcriptomic landscape of granulosa cells and peripheral blood mononuclear cells in women with PCOS compared to young poor responders and women with normal response. Hum Reprod. 2022 May 30;37(6):1274-1286. doi: 10.1093/humrep/deac069. |
| 34545401 | Result | Jiang Z, Shi C, Han H, Wang Y, Liang R, Chen X, Shen H. Mitochondria-related changes and metabolic dysfunction in low prognosis patients under the POSEIDON classification. Hum Reprod. 2021 Oct 18;36(11):2904-2915. doi: 10.1093/humrep/deab203. |