Possible Action of Resveratrol in Improving the Outcomes of IVF/ICSI in Couples With Unexplained Infertility

NCT06481696 | Recruiting

• 1 other identifier: ANDROS-01-24
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

Based on available evidence and given the potential beneficial effects of resveratrol in folliculogenesis and in oocyte development, the investigators designed a randomized, controlled, double-blind, single-center trial, whose objective will be the comparison of biological and clinical outcomes of resveratrol supplement in women undergoing IVF/ICSI cycles for unexplained infertility. To the knowledge of the investigators, no study has been published on the potential effect of resveratrol on IVF/ICSI outcomes considering couples with this infertility diagnosis, which may be the natural target of this integrative treatment because the process of folliculogenesis and oocyte maturation cannot be routinely investigated. An alteration of these biological mechanisms could be the unrecognized cause of part of the unexplained infertility and treatment with resveratrol could result in significant clinical improvement for the patients enrolled in the study. In more details, the main objective of this randomized, placebo-controlled, double-blind, single-center trial will be the evaluation of the possible effect of resveratrol in determining a better follicle development in patients with unexplained infertility undergoing controlled ovarian stimulation (COS) for IVF/ICSI. Infertile female patients with normal ovarian reserve will be treated according to clinical practice and the difference between expected (through AFC) and retrieved oocytes will be assessed in relation to use of resveratrol.

Conditions

Unexplained Infertility

Outcome Measures

Primary Outcomes (4)

• FORT (Follicle Output Rate)

  It is defined as the ratio of pre-ovulatory follicle (≥ 16 mm in diameter) count (PFC) on the day of induction of oocyte maturation and the antral follicle count at baseline, multiplied by 100 (higher values indicate a better outcome).

  The assessment will be performed at the end of stimulation (11°-15° day of a menstrual cycle of 28 days)

• FOI (Follicle to Oocyte Index)

  It is defined by the ratio between the total number of oocytes collected at oocyte pick up and the number of antral follicles at baseline, multiplied by 100. FOI ≤ 50% is considered low (range 0-100%).

  The assessment will be performed at the end of oocyte pick up (2 hours after the oocyte pick up)

• The number of mature oocytes

  The number of oocytes which have completed the metaphase-II division

  The assessment will be performed after the oocyte pick up (2 hours after the oocyte pick up)

• OSI (Ovarian Sensitivity Index)

  It is defined by the ratio between the number of retrieved oocytes and total dose of gonadotropins administered, multiplied by 1000.

  The assessment will be performed at the end of oocyte pick up (2 hours after the oocyte pick up)

Secondary Outcomes (2)

• Fertilization rate

  The assessment will be carried out the day after the insemination (one day after the oocyte pick up).

• Cumulative Clinical Pregnancy Rate

  The assessment will be carried out at 7th week of amenorrhea.

Study Arms (2)

Resveratrol group

ACTIVE COMPARATOR

Treatment with resveratrol, folic acid and vitamins B6, B12, D. The duration of treatment will be at least 65 days before the starting of stimulation (from the stage of pre-antral follicles) and until the day of oocyte pick up.

Dietary Supplement: Resveratrol-based multivitamin supplement; Procedure: IVF/ICSI; Drug: Follitropin Alfa; Drug: Ganirelix Acetate 0.5 MG/ML [Fyremadel]; Drug: hCG 10.000 IU or triptorelin 0,3 mg, subcutaneously

Placebo group

ACTIVE COMPARATOR

Treatment with folic acid only. The duration of treatment will be at least 65 days before the starting of stimulation (from the stage of pre-antral follicles) and until the day of oocyte pick up.

Dietary Supplement: Folic acid; Procedure: IVF/ICSI; Drug: Follitropin Alfa; Drug: Ganirelix Acetate 0.5 MG/ML [Fyremadel]; Drug: hCG 10.000 IU or triptorelin 0,3 mg, subcutaneously

Interventions

Resveratrol-based multivitamin supplement DIETARY_SUPPLEMENT

Natural polyphenol and vitamins

Also known as: Genante

Resveratrol group

Folic acid DIETARY_SUPPLEMENT

Supplementation with folic acid at the standard dosage of 0.4 mg/die

Placebo group

IVF/ICSI PROCEDURE

In vitro fertilization/IntraCytoplasmic Sperm Injection

Also known as: In vitro fertilization

Placebo group; Resveratrol group

Follitropin Alfa DRUG

Controlled Ovarian Stimulation

Also known as: Gonal-F

Placebo group; Resveratrol group

Ganirelix Acetate 0.5 MG/ML [Fyremadel] DRUG

GnRH Antagonist

Placebo group; Resveratrol group

hCG 10.000 IU or triptorelin 0,3 mg, subcutaneously DRUG

For the induction of oocyte maturation

Also known as: Gonasi or Decapeptyl

Placebo group; Resveratrol group

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Female age 18-40 years
• Female BMI 18-30 kg/m2
• normal menstrual cycles (26-35 days)
• duration of infertility at least 18 months
• normal semen parameters as established by WHO laboratory manual for the examination and processing of human semen Sixth edition
• normal US evaluation of male genital anatomy
• normal FSH, LH, Prolactin, Total Testosterone, Estradiol in male partner
• bilateral tubal patency established by 3-D HyFoSy or HSG
• normal uterine cavity evaluated by 3-D HyFoSy or HSG or hysteroscopy
• absence of antibodies Anti-Chlamyidia Trachomatis IgG/IgM
• failed intrauterine inseminations or couple's decision to refuse intrauterine inseminations

You may not qualify if:

• ≥15 cigarettes per day at least in one of the partners
• irregular menstrual cycles
• poor ovarian response (on the basis of the "Bologna" Criteria)
• inaccessible ovaries
• severe endometriosis (stage III-IV of the ASRM revised classification)
• significant systemic diseases
• heterologous fertilization
• previous pelvic surgery
• presence of ovarian cysts
• polycystic ovary syndrome
• use of hormonal contraception in the previous 3 months
• use of gonadotrophins in the previous 3 months
• III stage varicocele

Sponsors & Collaborators

• Andros Day Surgery Clinic: lead

Study Sites (1)

ANDROS Day Surgery Clinic

Palermo, 90144, Italy

RECRUITING

Related Publications (7)

• Gerli S, Della Morte C, Ceccobelli M, Mariani M, Favilli A, Leonardi L, Lanti A, Iannitti RG, Fioretti B. Biological and clinical effects of a resveratrol-based multivitamin supplement on intracytoplasmic sperm injection cycles: a single-center, randomized controlled trial. J Matern Fetal Neonatal Med. 2022 Dec;35(25):7640-7648. doi: 10.1080/14767058.2021.1958313. Epub 2021 Aug 1.

  PMID: 34338114 RESULT

• Han Y, Luo H, Wang H, Cai J, Zhang Y. SIRT1 induces resistance to apoptosis in human granulosa cells by activating the ERK pathway and inhibiting NF-kappaB signaling with anti-inflammatory functions. Apoptosis. 2017 Oct;22(10):1260-1272. doi: 10.1007/s10495-017-1386-y.

  PMID: 28755171 RESULT

• May-Panloup P, Chretien MF, Malthiery Y, Reynier P. Mitochondrial DNA in the oocyte and the developing embryo. Curr Top Dev Biol. 2007;77:51-83. doi: 10.1016/S0070-2153(06)77003-X.

  PMID: 17222700 RESULT

• Ortega I, Duleba AJ. Ovarian actions of resveratrol. Ann N Y Acad Sci. 2015 Aug;1348(1):86-96. doi: 10.1111/nyas.12875.

  PMID: 26315293 RESULT

• Ragonese F, Monarca L, De Luca A, Mancinelli L, Mariani M, Corbucci C, Gerli S, Iannitti RG, Leonardi L, Fioretti B. Resveratrol depolarizes the membrane potential in human granulosa cells and promotes mitochondrial biogenesis. Fertil Steril. 2021 Apr;115(4):1063-1073. doi: 10.1016/j.fertnstert.2020.08.016. Epub 2021 Jan 22.

  PMID: 33487442 RESULT

• Guideline Group on Unexplained Infertility; Romualdi D, Ata B, Bhattacharya S, Bosch E, Costello M, Gersak K, Homburg R, Mincheva M, Norman RJ, Piltonen T, Dos Santos-Ribeiro S, Scicluna D, Somers S, Sunkara SK, Verhoeve HR, Le Clef N. Evidence-based guideline: unexplained infertilitydagger. Hum Reprod. 2023 Oct 3;38(10):1881-1890. doi: 10.1093/humrep/dead150.

  PMID: 37599566 RESULT

• Cox CM, Thoma ME, Tchangalova N, Mburu G, Bornstein MJ, Johnson CL, Kiarie J. Infertility prevalence and the methods of estimation from 1990 to 2021: a systematic review and meta-analysis. Hum Reprod Open. 2022 Nov 12;2022(4):hoac051. doi: 10.1093/hropen/hoac051. eCollection 2022.

  PMID: 36483694 RESULT

MeSH Terms

Interventions

Folic Acid; Fertilization in Vitro; follitropin alfa; ganirelix; Triptorelin Pamoate

Intervention Hierarchy (Ancestors)

Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Reproductive Techniques, Assisted; Reproductive Techniques; Therapeutics; Investigative Techniques; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Adolfo Allegra, MD

  ANDROS Day Surgery Clinic Palermo, Italy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Adolfo Allegra, MD

CONTACT

0039 091 6785535; adolfo.allegra@clinicaandros.it

Angelo Marino, MD

CONTACT

0039 091 6785539; angelo.marino@clinicaandros.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2024
• First Posted: July 1, 2024
• Study Start: June 1, 2024
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: July 1, 2024

Record last verified: 2024-06

Locations

IT (1)