Clinical Application of In Vitro Maturation of Oocytes

*Xiaolin La, Jing Zhao and Zhihui Wang*

## **Abstract**

In vitro maturation (IVM) is a technique used to induce immature oocytes collected in different periods of embryonic growth. The rates vary for immature oocytes collected from different clinical sources to potentially develop into embryos and achieve live birth. As an effective treatment method, IVM can be used to treat patients with polycystic ovary syndrome (PCOS), ovarian hyperresponsiveness, and hyporesponsiveness, as well as to preserve the fertility of cancer patients. This technology has been used worldwide for the birth of thousands of healthy babies. The improvement in clinical IVM technology mainly focuses on the IVM medium and the optimization of the culture environment and operation process. At present, with the improvement in the in vitro fertilization (IVF) efficiency and culture systems, a natural cycle or mild stimulation may be more suitable for women receiving IVF treatments. A new treatment option was proposed to combine natural cycle/ mild stimulation IVF with IVM. In particular, the combination of mild stimulation IVF and IVM is not only expected to become a viable alternative to current standard treatments but may also become a potential option of first-line treatment.

**Keywords:** in vitro maturation (IVM), assisted reproductive technologies (ARTs), cytoplasmic maturation, antral follicles, granulosa cells

### **1. Introduction**

In the 1960s, major milestones were achieved in in vitro maturation (IVM) of human oocytes, and in vitro fertilization (IVF) of IVM oocytes was also established. Therefore, modern assisted reproductive technologies (ARTs) are based on IVM. Currently, the clinical application of IVM may be extended to treat patients with polycystic ovary syndrome (PCOS), ovarian hyperresponsiveness, and hyporesponsiveness, as well as to preserve the fertility of cancer patients [1]. In 2013, the practice committees of the American Society for Reproductive Medicine (ASRM) and the Society for Assisted Reproductive Technology (SART) stated that the clinical pregnancy rate of IVM was still lower than that of conventional IVF, and hence IVM could not yet be considered the first treatment choice for all cases of female infertility [2].

The current standard protocol for ovulation induction in clinical practice involves intense stimulation with nonphysiological doses of gonadotropins to obtain an average of 10–15 or even dozens of mature oocytes per woman. Although the regimen of high-dose gonadotropin treatment may enable the retrieval of a larger number of oocytes, this approach can exert several short- and long-term adverse effects, including the risk of ovarian hyperstimulation syndrome (OHSS).

At present, with the improvement in the IVF efficiency and culture systems, a natural cycle or mild stimulation may be more suitable for women receiving IVF treatments. A previous study showed that natural cycle or mild stimulation IVF is more effective than conventional stimulation protocols in patients with a low functional ovarian reserve [3]. In contrast to the standard stimulation protocol, the mild stimulation protocol is a safer and more rational regimen that helps reduce the hormone dosage, lower treatment risks, and retrieve a small number of high-quality oocytes. Despite these theoretical advantages, the mild stimulation protocol has yet to become a mainstream treatment modality in the United States. With the development of IVM technology, a modified protocol able to increase the success rates of natural cycle or mild stimulation IVF has been established. In this protocol, in addition to the retrieval of mature oocytes in naturally or mildly stimulated cycles, immature oocytes from small follicles are also retrieved for IVM, thereby increasing the total number of retrieved oocytes in a single treatment cycle and the clinical pregnancy rate. Data from previous clinical studies has shown that the combined use of natural cycle or mild stimulation IVF with IVM can expand the applicable scope of IVM technology to the treatment of various types of female infertility and has resulted in satisfactory clinical pregnancy rates and live birth rates [4, 5].
