Clinical trial NCT06617988: SIRT3 Expression in Granulosa Cells and the Levels of Follicular Fluid Metabolites Among POR Subgroups
Official title: Investigate Differences in SIRT3 Expression in Granulosa Cells and the Levels of Follicular Fluid Metabolites Among Poor Ovarian Responders Subgroups, and Their Association with IVF Outcomes.
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Poor Ovarian Response
Keywords: Poor ovarian response
In vitro fertilization and embryo transfer
Sirtuin-3
mRNA expression
Lead sponsor: Shandong University of Traditional Chinese Medicine
Sponsor class: OTHER
First posted: 2024-10-01
Enrollment: 80
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 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.

Brief summary: 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:

1. Can the relative expression level of SIRT3 differentiate between POR subtypes, and do these differences reflect distinct metabolic characteristics among the subtypes?
2. Investigate whether SIRT3 expression levels correlate with clinical outcomes. This study will enroll patients with various POR subtypes and collect discarded follicular fluid and granulosa cells on the day of egg retrieval. IVF outcome information routinely collected in electronic databases will also be recorded. Notably, this is a purely observational study with no additional interventions. Your participation will not alter your clinical treatment compared to other patients.


Eligibility criteria: Inclusion Criteria:

* 1. Women who are married and aged between 20 to 45 years, diagnosed with infertility;
* 2. Individuals undergoing their first or second cycle of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), with a scheduled fresh embryo transfer;
* 3. Participants must fulfill the diagnostic criteria corresponding to one of the following prognostic categories as determined by the clinician: Normal prognosis, unexpected poor prognosis, poor prognosis of advanced maternal age, or expected poor prognosis.

Exclusion Criteria:

* 1. A body mass index (BMI) of ≥ 35 kg/m²;
* 2. Participation in cycles involving pre-implantation genetic testing or diagnosis of embryos;
* 3. Involvement in cycles utilizing frozen gametes;
* 4. Engagement in cycles that employ donor-derived oocytes;
* 5. Participation in in vitro maturation cycles;
* 6.The presence of uterine cavity or endometrial abnormalities, including but not limited to fibroids, endometrial polyps, malformations, adenomyomas, endometritis, endometrial thinning, hydrosalpinx, uterine infections;
* 7.The existence of contraindications to assisted reproductive technology or pregnancy, such as uncontrolled liver or kidney dysfunction, diabetes mellitus (with glycated hemoglobin ≤ 7% and fasting blood glucose \&amp;amp;amp;lt; 10 mmol/L), hypertension, thyroid disorders, asymptomatic cardiac conditions, moderate-to-severe anemia, malignancies, a history of thromboembolism or thrombosis, severe mental health disorders, acute infections of the urinary and reproductive systems, sexually transmitted infections, and detrimental lifestyle factors including substance abuse. Additionally, exposure to teratogenic levels of radiation, toxins, or medications (such as prednisone, other hormones, adrenaline, antibiotics, or medications for hypertension, cardiovascular issues, or antiviral treatment) during surgical procedures, as well as any physical conditions rendering pregnancy inadvisable, are also considered disqualifying factors.

Primary outcomes:
measure: The relative expression level of SIRT3 mRNA of granulosa cells
timeFrame: Detected within three days after oocyte retrieval
Secondary outcomes:
measure: Positive pregnancy rate
timeFrame: 2 weeks after the day of embryo transfer
measure: Embryo implantation rate
timeFrame: 3 weeks after the day of embryo transfer
measure: Clinical pregnancy rate
timeFrame: 4 weeks after the day of embryo transfer
measure: Number of oocytes retrieved
timeFrame: Within 1 day after the oocyte retrieval
measure: Average daily dose of gonadotropin per COS cycle
timeFrame: Through the process of controlled ovarian stimulation, an average of 10 days
measure: Total dosage of gonadotropin per COS cycle
timeFrame: Through the process of controlled ovarian stimulation, an average of 10 days
Other outcomes:
measure: Levels of follicular fluid metabolites
timeFrame: Detected within three days after oocyte retrieval
Locations:
city: Jinan
country: China
facility: Affiliated Hospital of Shandong University of Traditional Chinese Medicine
state: Shandong
Study officials:
affiliation: Shandong University of Traditional Chinese Medicine
name: Zhen-Gao Sun, M.D
role: PRINCIPAL_INVESTIGATOR
References:
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citation: 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.
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