In recent years, assisted reproductive technologies have developed rapidly. In particular, improvements in controlled ovarian stimulation protocols allowed the development of multiple synchronized follicles in the same oocyte retrieval cycle, which helps patients achieve increased high-quality embryo and pregnancy rates. At present, among the numerous COH protocols, the long GnRH-a protocol is considered one of the most classical superovulation protocol. By binding to GnRH receptors, GnRH-a results in a dramatic decrease in the number of receptors on the pituitary surface, whereby the receptors lose response to endogenous and exogenous GnRH. After 14 days of GnRH-a, the pituitary gland reaches a state of down-regulation, avoiding the appearance of early-onset LH surge and promoting the synchronous development of follicles . However, given that the sensitivity to Gn stimulation is not completely consistent during superovulation, growth differences between developing follicles cannot be completely overcome. Therefore, asynchronous follicular development can still be clinically observed in some patients. The determination of the HCG day is complex due to asynchronous follicles and is a challenge regularly faced by doctors. The immature or postmature follicles in patients are frequently collected, which reduces the number of effective embryos and affects the final clinical outcomes.
In the natural cycle, the other follicles on the side of the ovary where the dominant follicle is located are smaller than the contralateral follicle, indicating that the presence of the dominant follicle may inhibit the growth of other non-dominant follicles [15, 16]. Follicular dominance consists of two primary components: indirect endocrine action and direct intra-ovarian regulation. The dominant follicle is able to secrete high concentrations of INH-B and E2, leading to small follicles atresia due to the down-regulation of FSH concentrations. The dominant follicle is more sensitive to FSH stimulation due to the increased number of granulosa cells and the increase of FSH receptors, which allows the dominant follicle to survive despite the later decrease in circulating FSH concentration. This process can be regarded as an indirect endocrine effect of the dominant follicle [3, 17]. In addition to this systemic endocrine factor, the dominant follicle can directly inhibit the growth and development of small follicles through paracrine and autocrine effects. The concentration of insulin-like growth factors-1 (IGF-1) is higher in the dominant follicle than in the small follicles, and the IGF-1 system can amplifie FSH and stimulate the growth of follicles. The presence of a dominant follicle allows increased IGF-binding protein (IGFBP) production on small follicles, thus reducing the concentration of available IGF-1. Therefore, the dominant follicle can continue growing despite reduced FSH concentrations, while the adjacent small follicles undergo follicular atresia and die [18, 19]. Additionally, Spears et al.  determined that the dominant follicle's effects were established when the follicles were cultured together, while this phenomenon did not arise when follicular clusters were cultured separately under similar conditions. Therefore, it is hypothesized that there is a direct interaction between the follicles, which allows the dominant follicle to influence the fate of the adjacent follicles by enhancing the endocrine dominance effect.
In clinical applications of the down-regulation protocol to induce superovulation, under the action of a high dose of FSH, the follicles developed in follicular clusters may still appear uneven in size. This phenomenon suggests that even if exogenous FSH can attenuate the indirect endocrine effect, the appearance of large dominant follicles will still affect the growth of the remaining small follicles due to internal regulation in the ovaries, which is, in turn, detrimental to clinical outcomes. In the ovine superovulation model, the dominant follicle influenced the number of follicles and embryos obtained from the ovary on the dominant follicle's side in ewes during high-dose FSH treatment and decreased embryonic viability as well . Semra Kahraman et al.  studied the impact of follicular dynamics on early human embryo development for the first time. They discovered that for follicles derived from homogenous cycles, the odds of obtaining top or good quality blastocysts were 1.370-fold higher than that of heterogeneous follicles. Therefore, follicular sizes and variable growth rates in IVF-ET cycle could affect early human embryonic development.
In superovulation cycles, puncture and aspiration were performed to remove oocytes and granulosa cell from the dominant large follicles. The dominant follicles disappeared, thereby eliminating its direct inhibition on the adjacent follicles through interfollicular interactions. After the steroid-rich follicular fluid was aspirated, the steroid hormone level in the circulation decreased. This avoids the asynchronous development of endometrial glandular epithelium and stroma caused by the premature rise of LH surge and progesterone, helping to improve the embryo implantation rate [22, 23]. Fisch et al.  reported on a 39-year-old woman with a poor response to repeated IVF, who had prematurely developed 27-mm dominant follicles punctured during superovulation treatment and found that the number of oocytes retrieved increased after the puncture, and a healthy pregnancy was eventually attained. Animal experiments have revealed that removing the dominant follicle in cows 48 h before hyperstimulation could promote follicular growth and increase the number of transferable embryos . Herein, we compared the clinical outcomes of large follicle puncture and aspiration in patients with asynchronous follicles during COH cycles in order to investigate whether large follicle puncture and aspiration were beneficial in clinical treatment.
In this study, compared with Group 2, the differences between the diameter of the dominant and secondary follicles in Group 1 were more significant, and for this reason, clinicians often prefer large follicle puncture and aspiration for such patients. After the removal of the dominant follicles by puncture, the remaining small follicles became the target of Gn medication. Therefore, patients in Group 1 needed longer Gn usage time and Gn dosage to enable small follicles to reach the standard size for the HCG day. Herein, it was determined that dominant follicles tended to be those that developed faster than the remaining adjacent small follicles. However, their development rate did not correspond to the Gn usage days. The short Gn administration time of the dominant follicles can affect the maturation of the cytoplasm. The expression of the nucleus mainly depends on the regulation of cytokines in the cytoplasm, and consequently, the immaturity of the cytoplasm can lead to defects in the quality and quantity of cytokines. Finally, the quality of follicles and embryos are badly affected . In addition, it was challenging to decide the HCG day in Group 2 due to the presence of dominant follicle. On the day of oocyte retrieval, only a few follicles met the diameter criterion for mature follicles. In contrast, the number of small follicles was high, implying that the oocyte maturation rate and high-quality embryo rate were lower than that of Group 1. However, there were no statistically significant differences between the two groups in the 2pn fertilization rate, clinical pregnancy rate, and live birth rate. This may be due to embryo formation and development is a complex and dynamic process. During the whole process of embryonic development, multiple factors, namely, the ultrastructure of oocytes and embryos, embryonic development potential, endometrial receptivity, etc., can affect normal fertilization, embryonic development, and ultimately, clinical pregnancy.
Son WY et al.  compared the pregnancy outcomes of IVM cycles in 160 patients and determined that in hCG-primed IVM cycles, ipsilateral immature oocytes were adversely affected when the diameter of dominant follicles exceeded 14 mm, and better clinical outcomes could be achieved by retrieving oocytes before the dominant follicles' diameter exceeded 14 mm. To determine whether large follicle puncture and aspiration affected the outcomes when the dominant follicles appeared at different time points, the 180 patients were tentatively divided into 4 subgroups based on whether the diameter of DF exceeded 14 mm on the day of their appearance and whether large follicle puncture and aspiration were performed. The results revealed that Subgroup A1 had a higher Gn dosage and total Gn usage time compared to Subgroup A2. Moreover, the oocyte maturation rate, high-quality embryo rate, and live birth rate were significantly better in Subgroup A1 than Subgroup A2. However, no significant differences were observed in Subgroup B1 than Subgroup B2. The results demonstrated that when the diameter of the dominant follicles that appeared did not exceed 14 mm, clinicians could perform large follicle puncture and aspiration to improve the pregnancy outcomes. For patients with dominant follicles greater than 14 mm, no special treatment was required, and the hyperovulation protocol could proceed. Large follicle puncture and aspiration did not result in practical benefits for these patients and might instead increase their economic and psychological burdens. However, this results contradict the findings of Son WY. If ipsilateral immature oocytes were adversely affected when the dominant follicles exceeded 14 mm, the large follicle puncture would be more beneficial for such patients. However, our experiment led to the opposite conclusion. Given the paucity of research on this subject and the small sample size included in this experiment, future studies should focus on expanding the sample size to provide more accurate results.