Purpose In this review, the current knowledge on anti-Müllerian hormone (AMH) is presented, concerning its value in disease and IVF treatment as well as in terms of its prospective clinical use. Methods AMH is becoming the most appropriate biomarker for the ovarian reserve measured predominantly for assisted reproductive treatment (ART) patients in comparison to the currently used antral follicle count (AFC). However, this is not the only way AMH measurements can be used in the clinics. Because of this, we reviewed the current literature for the use of AMH in current or prospective clinical practice. Results We found that AMH has a high predictive value in assessing the ovarian reserve, which can lead to a better efficiency of in vitro fertilization (IVF) procedures. It has a high potential to be developed as a staple diagnostic marker of ovarian disease, especially for ovarian cancers and even as a possible treatment tool for certain cancers. It could potentially be used to prevent oocyte loss due to chemo-or radiotherapy. Conclusion AMH is an important hormone especially in women reproductive organs and is currently seen as the best biomarker for a multitude of uses in reproductive medicine. Currently, the biggest issue lies in the lack of international standardization of AMH. However, it is encouraging to see that there is interest in AMH in the form of research on its action and use in reproductive medicine.

Oxidative stress in the follicular fluid (FF) is thought to be responsible for the abnormal development of oocytes. In our study patients with polycystic ovarian syndrome (PCOS), endometriosis, and tubal infertility factor (TIF), and healthy women with a male factor of infertility, were prospectively enrolled. From each patient, a sample of individual FF was collected from a dominant follicle. Concentration levels of TAS, 8-IP, 8-OHdG, and AMH were determined. In women with PCOS, we found significantly lower values of oxidative stress markers in the FF. 8-IP and TAS levels were lower in the FF of women with endometriosis. In women with TIF, we also found significantly lower values of all tested markers in the FF, except for 8-OHdG and AMH. We wanted to see whether the biomarker measured in the FF in an individual diagnosis could predict a successfully obtained embryo from this particular follicle. The FF 8-OHdG result in PCOS patients stood out and proved to be a good predictive marker of matured and fertilized oocytes in these patients. Further research is needed to be able to apply the acquired knowledge in improving the outcome of IVF procedures.

Background The aim of this study was to determine whether in vitro maturation (IVM) of immature oocytes after controlled hormonal stimulation of the ovaries could be important in cancer patients to improve their chances of conception in the future. Patients and methods After ovarian stimulation in cancer patients, the number of oocytes and their quality and maturity were compared to control patients with fertility problems in the in vitro fertilization (IVF) program. In both groups of patients, immature oocytes at the developmental stage of germinal vesicle were matured in vitro and the proportion of oocytes that matured in vitro was compared between groups. In a subset of women with fertility problems, intracytoplasmic sperm injection (ICSI) was performed on IVM oocytes to assess their ability to be fertilized and develop into an embryo compared to vivo matured oocytes in the same cycles and consider the procedure in cancer patients. Results In patients with different cancers, the disease did not affect the number and quality of retrieved oocytes. In cancer patients, there was even a significantly lower proportion of immature oocytes than in patients with fertility problems (30.0% vs. 43.6%; P < 0.05). However, in patients with cancer, fewer oocytes per patient matured in vitro than in patients with fertility problems (1.39 ± 1.04 vs. 2.48 ± 1.83; P < 0.05). After ICSI, the proportions of fertilized oocytes and fertilized oocytes developing into an embryo did not differ between oocytes matured in vitro and in vivo in the same cycles. Conclusions Oocyte IVM is proving to be a reliable procedure for resolving immature oocytes after controlled ovarian stimulation in cancer patients.

Study question Does the addition of recombinant AMH to the in vitro maturation (IVM) medium improve the maturation of GV oocytes after controlled ovarian hormonal stimulation? Summary answer Our results show that the addition of recombinant AMH to the in vitro maturation medium improves the maturation rate of GV oocytes. What is known already Anti-Müllerian hormone (AMH) is an important hormone involved in the process of sex differentiation during embryonic development. At the transition to the 21. century, more and more researchers have studied the role of AMH in ovarian function, especially its impact on folliculogenesis. AMH is becoming one of the main biomarkers of ovarian reserve and ovarian-specific disease, however, little is known about its effect on human oocyte maturation. Therefore, we matured immature GV (germinal vesicle) oocytes in IVM medium with recombinant AMH to assess its effect compared to the conventional IVM procedure with FSH and hCG. Study design, size, duration In this two-year prospective study, we compared the maturation rate of four groups of immature (GV) oocytes matured in maturation medium with added i) AMH (n = 15), ii) AMH+FSH+hCG (n = 44), iii) FSH+hCG (conventional; n = 22), and iv) hormone-free maturation medium (control; n = 15). Each oocyte was matured in vitro for a maximum of 28 hours and monitored by time-lapse microscopy to assess the time of GV breakdown (MI) and extrusion of the polar body (MII). Participants/materials, setting, methods Ninety-six GV oocytes of 46 patients (aged &lt; 38 years, involved in the ICSI programme) after short antagonist protocol of controlled ovarian hormonal stimulation were included after written informed consent. IVM of oocytes was performed in the MediCult IVM System (LAG and IVM medium, Cooper Surgical, Denmark) with added hormones, and in a CO2 incubator equipped with the PrimoVision time-lapse microscope (Vitrolife, Sweden). Main results and the role of chance IVM medium with added recombinant AMH gave the best result with all (100 %) oocytes matured in vitro. In conventional IVM medium with FSH and hCG, the oocyte maturation rate was poorer, with 68 % of oocytes matured in vitro. An even lower oocyte maturation rate (34 %) was observed in IVM medium with AMH, FSH and HCG, which might be explained by the antagonistic action of these hormones. In a group of control oocytes, 25 % of oocytes matured in vitro. The mean time to GV breakdown (MI stage) was 3.7 hours and to polar body release (MII stage) 20,5 hours. The time to MI stage was quite comparable in all groups of oocytes (3.5, 3.8 and 3.7 hours). There was a tendency for the polar body to be released later if AMH was added to the maturation medium (21.5 and 20.2 vs. 19.9 hours) but differences were not statistically significant, as revealed by Student’s t-test. In the control group of oocytes, these times were prolonged (4.2 and 22.2 hours) due to slow spontaneous maturation. These preliminary results demonstrate that AMH could directly affect the oocyte maturation in vitro. Limitations, reasons for caution The limitation is the relatively small number of oocytes included; GV oocytes accounted for less than 10 % of all oocytes in the in vitro fertilisation (ICSI) programme. Moreover, the proportion of GV oocytes spontaneously matured to MI stage before the start of the experiment and were therefore not included. Wider implications of the findings Based on our data, we believe that AMH directly affects human oocyte maturation in vitro. Despite the common knowledge that AMH regulates the recruitment of growing ovarian follicles, it appears that the addition of AMH to the maturation medium can improve the human oocyte maturation in vitro. Trial registration number 0120-546/2018/6

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