Follicle development and its prediction in patients with primary ovarian insufficiency: Possible treatments and markers to maximize the ability to conceive with residual follicles

Abstract

Background: Primary ovarian insufficiency (POI) is characterized by the development of hypergonadotropic hypogonadism before 40 years of age and leads to intractable infertility. Although in vitro fertilization and embryo transfer with donated eggs enables pregnancy, not a few patients desire pregnancy using their oocytes. However, follicular development is rare and unpredictable in patients with POI. Thus, there is a need for treatments that promote the development of residual follicles and methods to accurately predict infrequent ovulation.

Methods: This review discusses the effects of various treatments for obtaining eggs from POI patients. Furthermore, this study focused a potential marker for predicting follicular growth in patients with POI.

Main findings: Different treatments such as hormone-replacement therapy, dehydroepiandrosterone supplementation, platelet-rich plasma injection, and in vitro activation have shown varying degrees of effectiveness in retrieving oocytes from patients with POI. To predict follicle development in the cycle, elevated serum estradiol and reduced follicle-stimulating hormone (FSH) levels are important. However, these markers are not always reliable under continuous estradiol-replacement therapy. As a novel marker for predicting follicle growth, serum anti-Müllerian hormone (AMH) levels, measured using the picoAMH enzyme-linked immunosorbent assay, were found to predict follicle growth in patients and the cycle.

Conclusion: This review highlights the challenges and available interventions for achieving pregnancy using a patient's oocytes in cases of POI. We believe that a combination of currently available treatments and prediction methods is the best strategy to enable patients with POI to conceive using their own eggs. Although AMH levels may predict follicle growth, further research is necessary to improve the chances of successful follicular development and conception in patients with POI.

Keywords: anti‐Müllerian hormone; enzyme‐linked immunosorbent assay; hypogonadism; premature ovarian failure; primary ovarian insufficiency.

FIGURE 1

Schematic model of the residual follicle pool and serum AMH levels; comparison of age‐dependent decline in women with normal cycles and with women POI. The upper panel shows the model for women with normal cycles: residual follicles decrease with age, accompanied by a decrease in serum AMH levels. The lower panel shows the model for women with POI: the residual follicle pool is smaller than that in age‐matched women with normal cycles. Consequently, serum AMH levels were low from an early stage of reproductive life. If there are cycles where small follicles develop, it is supposed that trace amounts of AMH can be detected in the serum (red arrow).

FIGURE 2

Serum AMH levels in patients with amenorrhea with or without follicle growth cycles. Patients with follicle growth showed significantly higher levels of serum AMH. Bars represent the medians. This figure has been reproduced with permission from “Reproductive Sciences volume 23, pages 756–760 (2016).”