Effect of Astaxanthin on Advanced Glycation End Products (AGE)-Receptor for AGE (RAGE)-Inflammation Signaling pathway in Women with Polycystic Ovarian Syndrome-Associated Infertility

Determination of the effect of Astaxanthin on AGE-RAGE-Inflammation signaling pathway in women with PCOS-associated infertility

This study was designed as a randomized, double-blind, placebo-controlled, phase 3 clinical trial on 44 patients including two parallel groups (22 intervention and 22 placebo).

This study will be conducted at the Omid Fertility Center in Tehran. All participants will start allocated intervention (astaxanthin or placebo) from the first day of menstruation and will continue until OPU. Participants and outcome assessors will be unaware of the type of interventions. On the third day of the next menstrual bleeding, 300-150 IU of recombinant follicle-stimulating hormone will be administered daily. When at least 2 follicles with a size of 12-13 mm are detected, the antagonist will be started. After the detection of 18 mm mature follicles, 10,000 IU human chorionic gonadotropin (hCG) will be administered. Follicles will be retrieved 36 hours after hCG injection and follicular fluid will be preserved for granulosa cell isolation.

Women aged 20 to 35 with an anovulatory infertility due to PCOS and risk of ovarian hyperstimulation syndrome (OHSS) will be included. Women with a history of endocrinopathies or other causes of infertility and taking other supplements, hormonal agents, and metformin will not be included.

Astaxanthin group: daily intake of 12 mg of astaxanthin for 6 weeks until the day before ovarian puncture (OPU). Control group: daily consumption of placebo capsules completely similar to astaxanthin for 6 weeks until the day before OPU

Incidence of OHSS as the primary outcome, and the levels of inflammatory cytokines in follicular fluid and the expression level of genes and proteins of the RAGE-NFkB signaling pathway as the secondary outcomes.

Adding information about the actual start and end dates of the study, modifying some of the inclusion criteria, and modifying the study outcomes.

Eligible participants will be randomized through a block randomization method. The size and number of blocks will be considered as 8 blocks of 4 and 3 blocks of 6. Designing the blocks and preparing the randomization list will be done by using a web-based online system (sealedenvelope.com). The random allocation list will be provided exclusively to the methodologist. To conceal the random allocation process, 44 envelopes will be numbered with a 10-digit random code, which is the drug identification number. The code recognition key will be only available to the methodologist. All envelopes will be placed in a box in the order and on the basis of the random allocation list and will be available to the corresponding member. When the gynecologist declares the patient's eligibility, the methodologist will provide the doctor with the envelope. The treatment plan (A or B) will be selected based on the type of treatment mentioned in the envelope.

Considering the similar appearance of the Astaxanthin and placebo as well as their similar packaging, the participants will be unaware of the group they are allocated. All outcome investigators (including embryologists, gynecologists, and researchers) will be unaware of the random allocation process and the type of treatments until the end of the study. Also, data sheets will be coded to blind the statistician who will analyze study findings.