Effects of Resveratrol Supplementation on Oocyte Quality

Effects of Resveratrol Supplementation on Oocyte Quality in Advanced Maternal Aged Women Undergoing in Vitro Fertilization.

The goal of this randomized, double-blind, placebo-controlled clinical trial is to verify if 3-month oral supplementation with resveratrol can enhance the oocyte quality in advanced maternal age women undergoing in vitro fertilization (IVF).

Participants will take a daily capsule of resveratrol or placebo during the 3 months preceding their IVF treatment. They will then follow the same treatment protocol as non-participant patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Infertility; Aging
• Intervention / Treatment: Dietary supplement: Resveratrol; Dietary supplement: Folic acid

Detailed Description

The study will be conducted in the Reproductive Medicine Unit of an Academic Hospital.

Eligible participants who meet the inclusion and exclusion criteria will be randomly assigned to one of the following groups:

1. Resveratrol (study group) or
2. Placebo (control group).

Supplementation

Women in the study group will take a daily capsule of 200 mg Polygonum cuspidatum (Solgar®, Dietimport, Lisboa, Portugal) yielding 100 mg/day resveratrol (trans-3,5,4'-trihydroxystilbene). Women from control group will take a daily capsule of 400 mcg folic acid (Solgar®, Dietimport, Lisboa, Portugal), a vitamin widely prescribed to women who intend to achieve pregnancy for prevention of neural tube defects). Participants will be instructed to take the capsules by morning, every day during the 3 months preceding their IVF treatment. Oral intake of resveratrol/placebo will be discontinued after oocyte retrieval due to the potential adverse effects of resveratrol on endometrial decidualization. Package of resveratrol and placebo will be identical. Compliance of the participant to the intervention will be measured using capsule count. Participants will be asked to keep their usual lifestyle including nutrition and physical activity level.

Ovarian stimulation

GnRH antagonist protocol will be used in all the patients. On day 2 or 3 of the menstrual cycle, daily subcutaneous (SC) injections of rFSH are given up to the day of human chorionic gonadotropin (hCG) administration, when at least three leading follicles reached a mean diameter of 17 mm. Doses of rFSH range from 150 to 300 IU/day depending on the women's age, body mass index (BMI), AFC and AMH. Administration of a daily dose of 0.25 mg of gonadotropin releasing hormone antagonist (GnRHa) (Cetrotide ®, Merck, Netherlands; or Orgalutran ®, Organon, Netherlands) is initiated when the larger follicle reaches a mean diameter of 14 mm. Transvaginal oocyte retrieval is scheduled to 36 hours after choriogonadotropin alfa (α-hCG) administration. Luteal phase support with progesterone is initiated on the day of the oocyte retrieval with 200 mg of micronized intravaginal progesterone every 8 hours (Progeffik ®, EFIKK, France).

In vitro fertilization and embryo transfer

According to the couples's indication, IVF or ICSI is performed. Fertilization is assessed after 18 hours, and oocyte maturational stage is assessed and registered. Embryo cleavage is assessed every 24 hours. Embryo transfer is performed 5 days after oocyte retrieval under ultrasound guidance. All remaining good quality embryos will be vitrified and transferred in subsequent menstrual cycles. If fresh transfer is canceled for clinical reasons, frozen embryo transfer will also be scheduled. Before frozen embryo transfer, patients will start exogenous hormone therapy for endometrial preparation. This therapy is initiated on day 1 of menstrual cycle and consists of 150 mcg of estradiol transdermal patches (Dermestril®, BGP, Lisboa, Portugal) replaced every 3 days. On day 12-14, a pelvic ultrasound is performed to assess endometrial development. If the endometrial thickness is > 7 mm, 400 mg vaginal micronized progesterone (Cyclogest®, Gedeon Richter, Budapest, Hungria) twice daily was added to the treatment scheme. Fourteen days after oocyte retrieval a quantitative serum value of β-hCG is obtained and a transvaginal ultrasound is scheduled one week later in case of a positive result (biochemical pregnancy). Clinical pregnancy is established by the ultrasonography visualization of a gestational sac. Ongoing pregnancy was defined by a viable intrauterine pregnancy of at least 12 weeks duration confirmed on an ultrasound scan. The outcomes of fresh and vitrified-warmed embryo transfer will be analyzed. Live birth was defined as the delivery of one or more live babies. Miscarriage was defined by a spontaneous pregnancy termination before the gestational age of 12 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 88
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Women with infertility undergoing IVF/ICSI
• Ovarian stimulation with GnRH-antagonist protocol
• Age 35-40 years old

Exclusion Criteria:

• Severe male factor (oligospermia or azoospermia)
• Low ovarian reserve (AMH < 1.1. ng/mL)
• Poor response to ovarian stimulation (< 3 oocytes)
• Polycystic ovarian syndrome (Rotterdam criteria)
• Ovarian endometriosis (endometrioma > 30 mm)
• Uterine anomalies (congenital or acquired)
• Diabetes Mellitus
• Concurrent use of any vitamin (except folic acid)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Resveratrol; Daily capsule of 200 mg Polygonum cuspidatum yielding 100 mg/day resveratrol (trans-3,5,4'-trihydroxystilbene)	Dietary supplement: Resveratrol; Daily capsule of 200 mg Polygonum cuspidatum (Solgar®, Dietimport, Lisboa, Portugal) yielding 100 mg/day resveratrol (trans-3,5,4'-trihydroxystilbene), by morning, every day during the 3 months preceding in vitro fertilization treatment.
Placebo Comparator: Placebo; Daily capsule of 400 mcg folic acid.	Dietary supplement: Folic acid; Daily capsule of 400 mcg folic acid (Solgar®, Dietimport, Lisboa, Portugal), by morning, every day during the 3 months preceding in vitro fertilization treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of good-quality embryos	Embryos available to transfer or cryopreservation.	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of oocytes and mature oocytes	Total oocytes and metaphase-II oocytes retrieved.	4 months
Fertilization rate	Percentage of oocytes with two pronuclei by the number of COCs retrieved)	4 months
Cleavage rate	Percentage of 2-cell stage embryos by the number of COCs retrieved	4 months
Biochemical pregnancy rate	Percentage of positive B-hCG in serum by initiated cycle	up to 15 months
Clinical pregnancy rate per cycle	Proportion of positive clinical pregnancies by initiated cycle	up to 15 months
Clinical pregnancy rate per embryo transfer	Proportion of positive clinical pregnancies by embryo transfer	up to 15 months
Ongoing pregnancy rate	Proportion of ongoing pregnancies (viable intrauterine pregnancy of at least 12 weeks)	up to 15 months
Cumulate live birth rate	Number of deliveries with at least one live birth resulting from one initiated cycle	up to 15 months

Collaborators and Investigators

• Sponsor: Centro Hospitalar e Universitário de Coimbra, E.P.E.

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: January 14, 2024
• First Submitted That Met QC Criteria: January 30, 2024
• First Posted (Actual): January 31, 2024

Study Record Updates

• Last Update Posted (Actual): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: in vitro fertilization; resveratrol; oocyte quality
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infertility; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Micronutrients; Vitamins; Antioxidants; Vitamin B Complex; Hematinics; Folic Acid; Resveratrol
• Other Study ID Numbers: RA-01-23

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No