Clinical Efficacy Analysis of Resveratrol in the Treatment of Primary Ovarian Insufficiency
Phase: NA
Conditions: Primary Ovarian Insufficiency
Sponsor: Affiliated Hospital of Nantong University

Clinical Efficacy Analysis of Resveratrol in the Treatment of
Primary Ovarian Insufficiency
Date：May 16, 2022
Research Proposal Summary
Scheme number
LCYJ-B05
Scheme name
Clinical
effect
of
resveratrol
on
early
onset
ovarian
insufficiency
Version number/date
Version 2.1, May 16, 2022
Indications
POI
Test purpose
In order to evaluate the role of resveratrol in the occurrence
and development of a variety of ROS-related diseases
including POI/POF, and to clarify the clinical effect and
mechanism of resveratrol antioxidant therapy.
Research design
Prospective, multicenter, randomized, controlled clinical trial
design
Total number of cases
150
Number
of
research
centers
4
Study period
36 months
Research object
Diagnostic criteria：
The diagnostic criteria for premature ovarian insufficiency
(POI) refer to the “2017 Chinese Expert Consensus on
Clinical Diagnosis and Treatment of Premature Ovarian
Insufficiency” and “2016 Expert Consensus on Hormone
Supplementation
Therapy
for
Premature
Ovarian

Insufficiency”; including: (1) Age <40 years old; (2)
oligomenorrhea or amenorrhea for at least 4 months; (3) at
least 2 times serum basal follicle-stimulating hormone (FSH)
>25IU/L (interval > 4 weeks). Subclinical POI: FSH level is
15~25 IU/L, which is a high-risk group.
The diagnostic criteria for premature ovarian failure (POF)
refer to the “2017 Chinese Expert Consensus on Clinical
Diagnosis
and
Treatment
of
Premature
Ovarian
Insufficiency”, which refers to amenorrhea, FSH>40IU/L,
and decreased estrogen levels before the age of 40,
accompanied by varying degrees of perimenopause Stage
symptoms are the terminal stage of POI.
standard constrain:
1. Amenorrhea or oligomenorrhea at least 4 months and
two (>4 weeks interval) basal FSH≥10mIU/ml；
2. age<40 years old；
3. Informed consent, voluntary experiment.
Exclusion criteria:
1. Pregnant and lactating patients;
2. Patients with endometriosis, adenomyosis, endometrial
lesions (submucosal fibroids ,endometrial polyps, etc.) ,
uterine fibroids>4 cm or hysterectomy;
3. Patients with adrenal cortical hyperplasia or tumor；
4. Ovarian neoplasms patients；
5. Hydrosalpinx patients；
6. Hyperprolactinemia patients；
7. Patients who are participating in other clinical trials or

have participated in other clinical trials within the past three
months;
8. Patients with suspected or real history of alcohol and drug
abuse;
9.
Known
allergy
to
the
investigational
drug
or
its
components;
10. Other patients deemed unsuitable for participation in this
trial by the investigator.
Note: Patients who were receiving hormone replacement
therapy at the time of recruitment were required to take at
least a 3-month suspension of medication to participate in
this trial.
Trial
grouping
and
medication
1. POI patients group:
According to
the computer-generated
random sequence, eligible patients were randomly assigned to the
RES group and non-RES group according to 1: 1. POI IVF patients
were divided into two groups: the RES treatment group (group A) and
the non-RES treatment group (group B). Basal sex hormone and
anti-Muller tube hormone were administered on day 2/3 of the
menstrual cycle before treatment and 3 months after treatment. Antral
Follicle (AFC) was detected by transvaginal B-ultrasonography, and
basic sex hormones included follicle-stimulating hormone (FSH),
Luteinizing hormone (LH), Estradiol 2 (E2) and Testosterone (T).
2. Medication: Patients in group A received oral RES at 250mg
daily for three months, and those in the non-RES group received oral
vitamin E at 100mg daily for three months.
Treatment and follow-up
Course of treatment: Patients in group A received oral RES at
250mg daily for three months, and those in the non-RES group
received oral vitamin E at 100mg daily for three months. All
patients used microstimulation to superstimulate ovulation, and

clomiphene 50-150mg was taken orally from the 3rd to 5th day of
menstruation, once a day for a total of 5 days later, the sex
hormones and follicular diameter were checked, and 150-300IU
Gonadotropin (Gn) was added as appropriate to the night needle
day. After follicle maturation, 10000IU of Human Chorionic
Gonadotropin (HCG) was injected intramuscularly or 250ug
Ovidrel subcutaneously to induce ovulation. 36-38 hours later, a
vaginal ultrasound-guided puncture was performed to collect eggs.
Specific inspection items include:
1. The patient’s hormone levels (basal FSH, LH, E2, T) were
detected on day 2/3 of the menstrual cycle;
2. Anti-Mullerian hormone (AMH) was detected in patients on day
2/3 of the menstrual cycle;
3. The numbers of antral follicles (AFC) were recorded by B
ultrasound transvaginal;
4. Pregnancy was recorded at the outpatient follow-up for patients
with reproductive needs ;
5. Patients were routinely tested for blood routine (RBC, WBC,
PLT, HGB), liver function (ALT, AST) and renal function (BUN,
Cr), and recorded adverse events.
Note:
1. Basal follicle-stimulating hormone (FSH) ≥10mIU/ml at the
first visit, and if other inclusion criteria are met if the patient has a
history of testing with a baseline FSH ≥10mIU/ml in the past
(interval> 4 weeks), he or she can be included in this study and
drug therapy can be started; (Interval> 4 weeks) If the basic
FSH≥10mIU/ml has not been diagnosed, the patient is required to
visit the hospital again after 4 weeks. If the basic FSH is still
≥10mIU/ml, they can be included in this study and drug therapy

can be started.
2. For patients with regular menstrual periods, the basal FSH and
antral follicle count (AFC) should be followed up on the 2nd to
4th day of the menstrual cycle. If the patient has menstrual cramps
after the follow-up and has not exceeded the visit window, they
are required to re-examine on the 2nd to 4th day of the menstrual
cycle and record the examination data.
Study endpoint
Primary endpoint : FSH, LH
Secondary endpoints :
(1) FSH, LH, E2, T; (2) Antral follicle count (AFC); (3) Basal sex
hormones and Anti- Mullerian hormone (AMH) on day 2/3 of the
menstrual cycle; (4) Embryo laboratory indicators including number
of eggs harvested, number of MII eggs, normally fertilized number,
and number of good quality embryos; (5) Peripheral blood human
villous gonadotropin (HCG); (6) Clinical pregnancy rate (patients
with reproductive needs).
Security indicators
1. Blood routine (RBC, WBC, PLT, HGB) , liver function (ALT,
AST) and renal function (BUN, Cr) ;
2. Patient adverse events were recorded.