Abstract

Abstract Study question Whether and how iron overload in ovaries affects follicular development in patients with ovarian endometriosis? Summary answer Iron overload microenvironment that affects the growth and development of granulosa cells and oocytes, leading to fewer oocytes retrieved and decreased ovarian reserve. What is known already The presence of an endometrioma with the high levels of free iron, shows an adverse effect on the surrounding ovarian tissue as reflected by a reduced number of developing follicles and oocytes retrieved in in vitro fertilization cycles. However there is few published data available focusing on the potential risk of free iron in folliculogenesis of patients with endometrioma. This study aimed to identify the impact of intrafollicular iron on granulosa cells (GCs) and follicular development in ovarian endometrioma patients. Study design, size, duration The clinical data of 50 patients with unilateral ovarian endometriosis who underwent in vitro fertilization, intracytoplasmic sperm injection, and embryo transfer in the Reproductive Medicine Center of Sun Yat-sen Memorial Hospital from October 2019 to September 2021 were prospectively collected. Meanwhile, 50 infertile patients without endometriosis were selected as the control group; they were matched by age, duration of infertility, and body mass index. Participants/materials, setting, methods Ffollicular fluid and granulosa cells were collected.The clinical data of the two groups of infertile patients were compared. The iron ion in follicular fluid was detected by colorimetry,transferrin, eatrogen and the ferritin concentration in follicular fluid was detected by enzyme-linked immunosorbent assay. qPCR and Western blotting were used to detect the expression of iron homeostasis-related genes and proteins in luteinized granulosa cells. Oocyte retrieval rates, maturation and fertilization rates were analyzed. Main results and the role of chance There were no significant differences in baseline data, including age, duration of infertility, BMI, between the two groups. The AFC and AMH in the experimental group were significantly lower than that in the control group. The number of oocytes obtained in the experimental group was 8.35 ± 5.80 vs. 13.71 ± 5.62, P > 0.05. P = 0.003; and the average oocyte retrieval rate (68.56 ± 34.97% vs. 88.64 ± 23.11%, p = 0.032) was significantly lower than those in the control group. The concentration of an iron in the follicular fluid of the cystic ovary (63.63 ± 24.69 mg/L) was significantly higher than that of the healthy ovary (51.65 ± 13.80 mg/L) and the control ovary (39.23 ± 16.89 mg/L), P = 0.005. The levels of ferritin light chain and heavy chain were significantly higher but transferrin and estrogen were lower in the cystic ovary than in the healthy ovary and the control ovary. qPCR and Western blot results showed that the mRNA and protein expression of transferrin receptor 1, ferritin heavy chain, and ferritin light chain were significantly higher in the cystic ovary than in the healthy ovary and the control ovary. Limitations, reasons for caution For limitation of sampling, we could not obtain the information from human growing follicles, animal experiments would be involved in our subsequent study. Wider implications of the findings These results provide novel information suggesting that when surgical removal of the endometrioma is not an option, further investigation is needed to clarify whether and how the medical therapy may limit or slow the damage caused by endometrioma. Trial registration number not applicabl

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