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Not yet recruitingNCT06990685Updated May 25, 2025

Effect of Salidroside on Pregnancy Outcomes in High Childbearing Age Patients in Viro Fertilization

A Phase 2 interventional study of Salidroside in Salidroside, Randomized Controlled Trial and In Vitro Fertilization, sponsored by The Second Hospital of Shandong University. Not yet recruiting at 1 site in China. Open to female participants aged 35 Years to 39 Years. Per ClinicalTrials.gov, last updated 2025-05-25.

Sponsored by The Second Hospital of Shandong University · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
370
Allocation
Randomized
Ages
35 Years to 39 Years
Sex
Female
01

Study summary

With the decreasing of birth rate and population in our country, population problem has become a long-term and strategic problem. In addition to the decrease in the number of women of childbearing age and the impact of unmarried women, the increase in the incidence of reproductive disorders and the delay of marriage and childbearing are also important factors leading to the continuous decline of the birth population in China. Among them, ovarian aging is a key factor causing female fertility difficulties. Therefore, establishing an effective prevention and treatment strategy for ovarian aging is of great significance for improving female reproductive health and serving the national population strategy. Recently, several supplements have been found to promote folliculogenesis and improve oocyte quality. However, to date, there is no approved therapeutic agent for the treatment of ovarian aging. Therefore, it is urgent to develop effective strategies for the prevention and treatment of ovarian aging.

Salidroside is the main active component of Chinese medicine Rhodiola, and its content is highest in the root of rhodiola, which is also the main medicinal part. The main efficacy of salidroside in traditional Chinese medicine is to benefit qi, promote blood circulation, unblock pulse and relieve asthma. At the same time, in basic research, more and more experiments have shown that salidroside has a variety of pharmacological properties, including anti-hypoxia, anti-fatigue and anti-aging effects, anti-cancer, anti-inflammatory, anti-oxidation, antiviral and so on. These pharmacological effects suggest that salidroside may be an effective drug for the prevention and treatment of atherosclerosis, Parkinson's disease, Alzheimer's disease, pneumonia and other diseases. In terms of aging, it has been confirmed that salidroside supplementation can prolong the life span of pseudogill oryzias zhan and rescue premature aging of human skin fibroblasts, etc., which further confirms.

The aim of this study is to investigate the efficacy of salidroside as an adjuvant drug in improving the pregnancy outcomes of fresh embryo transfer in high childbearing age patients with poor ovarian response by comparing the pregnancy outcomes of fresh embryo transfer between salidroside group and blank control group. This pragmatic clinical study is expected to improve pregnancy outcomes of fresh embryo transfer cycles in women of advanced childbearing age with poor ovarian response.

Read the detailed description

With the continuous decline in China's birth rate and number of births in recent years, the population issue has become a long-term and strategic issue in China. In addition to the impact of the decrease in the number of women of childbearing age and the non-marriage, the increase in the incidence of reproductive disorders and the postponement of the age of marriage and childbearing are also important factors leading to the continuous decline in the number of births in China. Among them, ovarian aging is a key factor causing fertility difficulties in women. Therefore, it is of great significance to establish an effective ovarian aging prevention and treatment strategy to improve women's reproductive health and serve the national population strategy. Recently, studies have found that a variety of supplements can promote follicular genesis and improve oocyte quality. However, to date, there are no approved effective treatments for ovarian aging. Therefore, it is urgent to develop effective strategies for the prevention and treatment of ovarian aging. Salidroside is the most active ingredient of Rhodiola rosea in traditional Chinese medicine, and has the highest content in the root of Rhodiola rosea, which is also the main medicinal site. The main effects of salidroside in traditional Chinese medicine are to invigorate qi and blood, and to relieve asthma. At the same time, in basic research, more and more experiments have shown that salidroside has a variety of pharmacological properties, including anti-hypoxia, anti-fatigue and anti-aging effects, anti-cancer effects, anti-inflammatory effects, antioxidant effects, antiviral effects, etc. These pharmacological effects suggest that salidroside may be an effective drug for the prevention and treatment of atherosclerosis, Parkinson's disease, Alzheimer's disease, pneumonia and other diseases. In terms of aging, it has been confirmed that supplementation of salidroside can prolong the life of Pseudogill medaka and save the premature aging of human skin fibroblasts, which further confirms the anti-aging effect and potential application value of salidroside. In the process of clinical assisted reproduction, the proportion of elderly women has been increasing in recent years; Due to the significant decline of female ovarian function in middle age, the success rate of assisted reproduction in elderly women has always been at a low level. However, whether in animal model studies or in human tissue sections, it is generally believed that there are still a large number of follicles in the ovaries of middle-aged females or females that are sufficient to support reproductive activities, but because the physiological reasons for the decline of ovarian function in middle-aged women are unknown, the contradiction of abundant follicles but declining ovarian function in middle-aged women cannot be overcome.Recently, Zhang Hua's team in China used high-resolution ovarian organ imaging technology combined with genetically modified animal models, single-cell omics and drug screening to reveal that the ovaries have specific vascular degeneration in middle age, which leads to a decrease in ovarian blood supply, stunted follicle development, and ultimately a decline in fertility. Mechanistic studies have confirmed that ovarian vascular endothelial aging is the cause of ovarian vascular degeneration in middle age. Based on the above findings, through the screening of a large number of natural products, it was found that in vitro treatment of salidroside can improve the regeneration ability of follicular blood vessels without affecting the development of follicles. Continuous injection of salidroside in vivo can significantly improve the ability of ovarian angiogenesis in elderly mice, improve ovarian blood supply, and then promote follicle development, increase the quantity and quality of ovulation in advanced mice, and increase the number of births in elderly mice. The safety evaluation proved that salidroside treatment had no effect on the blood vessels of heart, kidney, liver and other organs, and long-term (12 months) monitoring showed that there was no abnormal organ development and tumor production in mice after salidroside treatment. Other teams, using different in vitro and in vivo models, have also found that salidroside supplementation can improve oocyte quality in mice or pigs. On the one hand, the addition of salidroside to oocytes cultured in vitro can improve the maturation, fertilization and development ability of oocytes of childbearing age by maintaining normal spindle/chromosome structure and mitochondrial function, including improving oocyte spindle/chromosome arrangement, mitochondrial and cortical particle distribution, mitochondrial membrane potential, and reducing reactive oxygen species. On the other hand, it can also improve the oocyte quality of reproductive elderly mice by enhancing mitophagy, including improving their oocyte genesis, maturation, fertilization and embryonic development potential. The above studies provide a solid theoretical basis for salidroside to improve the quality of female oocytes. In summary, salidroside can improve oocyte quality and fertility through a variety of mechanisms. However, current research is still limited to animal experiments, and in-depth clinical evidence is lacking. Therefore, it is necessary to further explore the effect of salidroside on ovarian function, promote the clinical transformation of basic research, and serve the national population strategy.

02

Conditions studied

  • Salidroside
  • Randomized Controlled Trial
  • In Vitro Fertilization
  • Assisted Reproductive Technology
03

In context

Lead sponsor

The Second Hospital of Shandong University is the lead sponsor of 35 studies on the registry; 17 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
35 Years to 39 Years
Sexes eligible
Female
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. Age ≥35 and \< 40 years old
  2. For the first or second cycle of IVF, ICSI or IVF with donor sperm
  3. According to the 2016 Poseton criteria for poor prognosis: the number of oocytes obtained in the previous routine ovulation induction protocol was 1-9, or AFC \< 5 or AMH \< 1.2ng/ml (measured within the past half year) in both ovaries.

Exclusion criteria

Exclusion Criteria:

  1. Patients with coagulation disorders
  2. Patients with previous abnormal uterine bleeding
  3. Combined with hydrosalpinx confirmed by B-ultrasound and HSG
  4. Uterine malformation (unicornuate uterus, septate uterus) or history of intrauterine adhesions
  5. Patients with previous spontaneous abortion ≥3 times
  6. Patients with to assisted reproductive technology or pregnancy
  7. Previous or current oral medication containing salidroside
  8. The controlled ovarian stimulation protocol included PPOS protocol, luteal phase ovulation induction protocol, and continuous stimulation protocol
Terms in these criteria, in plain language(1)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
370 participants (estimated)

Study arms

  • No intervention
    Control group

    Long protocol, short protocol, or antagonist protocol et al.

  • Experimental
    Experimental Group

    In the salidroside group, oral administration of rhodiola capsules (Xizang Gaoyuan 'an Biotechnology Development Co., LTD.) was started on the day of entering the COS cycle, once a day, 2 pills at a time, and the drug was stopped on the trigger day.

    Drug: Salidroside

Interventions

  • DrugSalidroside

    In the salidroside group, oral administration of rhodiola capsules (Xizang Gaoyuan 'an Biotechnology Development Co., LTD.) was started on the day of entering the COS cycle, once a day, 2 pills at a time, and the drug was stopped on the trigger day.

06

What researchers measure

Primary outcomes

  1. Ongoing pregnancy rate

    The number of continuous pregnancy cycles divided by the number of frozen embryo transfer cycles

    Time frame: from transplantation to delivery (assessed up to 40 weeks of gestation)

Secondary outcomes

  1. Clinical pregnancy rate

    The number of clinical pregnancy cycles divided by the number of transplantation cycles

    Time frame: from transplantation to delivery (assessed up to 40 weeks of gestation)

  2. Biochemical pregnancy rate

    The number of biochemical pregnancy cycles divided by the number of transplantation cycles

    Time frame: from transplantation to delivery (assessed up to 40 weeks of gestation)

  3. Live birth rate

    The number of live birth cycles divided by the number of transplantation cycles

    Time frame: from transplantation to delivery (assessed up to 40 weeks of gestation)

  4. Embryo implantation rate

    The ratio of the number of gestational sacs observed by ultrasound to the number of transplanted embryos

    Time frame: from transplantation to delivery (assessed up to 40 weeks of gestation)

  5. Early abortion rate

    The ratio of the number of spontaneous abortion cycles to the number of clinical pregnancy cycles within 12 weeks of gestation

    Time frame: from transplantation to abortion (assessed up to 12 weeks of gestation)

  6. Ectopic pregnancy

    The embryo implants and grows and develops anywhere other than the uterine cavity

    Time frame: from transplantation to delivery (assessed up to 40 weeks of gestation)

  7. Pregnancy loss

    Natural termination of clinical pregnancy or therapeutic induction of labor before 28 weeks of gestation

    Time frame: from transplantation to abortion (assessed up to 28 weeks of gestation)

  8. Stillbirth

    A baby without vital signs is delivered at 28 weeks or more of gestation

    Time frame: from transplantation to delivery (assessed up to 40 weeks of gestation)

  9. Preterm birth

    Delivery before 37 weeks of gestation

    Time frame: from transplantation to delivery (assessed up to 37 weeks of gestation)

  10. Gestational diabetes mellitus

    Abnormalities of glucose metabolism of different degrees that first occur and are discovered during pregnancy

    Time frame: from transplantation to delivery (assessed up to 40 weeks of gestation)

  11. Preeclampsia

    After 20 weeks of gestation, if a pregnant woman has a systolic blood pressure of ≥140 mmHg and/or a diastolic blood pressure of ≥90 mmHg, accompanied by any one of the following: urine protein quantification ≥0.3 g/24 h, or the urine protein/creatinine ratio ≥0.3, or random urine protein ≥(+)(the examination method when protein quantification is not performed unconditionally); There is no proteinuria but any one of the following organs or systems is involved: important organs such as the heart, lungs, liver, and kidneys, or abnormal changes in the blood system, digestive system, and nervous system, or the placenta and fetus are involved, etc.

    Time frame: from transplantation to delivery (assessed up to 40 weeks of gestation)

  12. Hypertension in Pregnancy

    Hypertension first occurred after 20 weeks of pregnancy, with a systolic blood pressure of ≥140 mmHg (1 mmHg=0.133 kPa) and/or a diastolic blood pressure of ≥90 mmHg; The urine protein test was negative

    Time frame: from transplantation to delivery (assessed up to 40 weeks of gestation)

  13. Premature rupture of membranes

    It refers to the spontaneous rupture of the fetal membranes before labor. According to the gestational age at which it occurs, it is divided into full-term fetal membranes and preterm premature rupture of fetal membranes

    Time frame: from transplantation to delivery (assessed up to 40 weeks of gestation)

  14. Placenta previa

    The lower edge of the placenta is adjacent to or covers the internal OS of the cervix

    Time frame: from transplantation to delivery (assessed up to 40 weeks of gestation)

  15. Placental abruption

    The placenta in its normal position partially or completely separates from the uterine wall before the fetus is delivered

    Time frame: from transplantation to delivery (assessed up to 40 weeks of gestation)

  16. Postpartum Hemorrhage

    Within 24 hours after the delivery of the fetus, the amount of blood loss in parturients with vaginal delivery is ≥500 ml, the amount of blood loss in parturients with cesarean section is ≥ 1,000 ml, or there are symptoms or signs of hypovolume after blood loss

    Time frame: Within 24 hours after childbirth

  17. Neonatal death

    Infants with vital signs at birth die within 28 days after birth

    Time frame: Within 28 days after birth

07

Study locations

1 site
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 25, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT06990685
Lead sponsor
The Second Hospital of Shandong University
Responsible party
Linlin Cui (Professor, The Second Hospital of Shandong University) — Principal investigator
First posted
May 25, 2025
Start date
Jun 1, 2025 (estimated)
Primary completion
Jan 2027 (estimated)
Completion
Dec 2027 (estimated)
Last update
May 25, 2025

Study contacts

Li Ge, M.D., Ph.D.
Contact
geli1128@163.com
+86 17660083087
Linlin Cui, M.D., Ph.D.
study chair · The Second Hospital of Shandong University, China

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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