Intermittent spontaneous ovulation in patients with premature ovarian failure: Three case reports and review of literature

Premature ovarian failure (POF) is the end-stage of a decline in ovarian function prior to the age of 40 years that involves symptoms associated with low estradiol (E2) levels and a minimal probability of pregnancy. This increases the physical and psychological burden experienced by young women of reproductive age, particularly with regards to over-diagnosis.Here, we report three cases (29, 22, and 33 years-of-age) diagnosed with POF after experiencing secondary amenorrhea for more than one year, serum levels of follicle-stimulating hormone (FSH) > 40 IU/L on two occasions with an interval of more than 4 wk, and negative progesterone withdrawal tests. All three patients were intermittently administered with drugs to create an artificial cycle. During the subsequent discontinuation period, the patients experienced intermittent follicular growth and spontaneous ovulation. One patient experienced two natural pregnancies (both with embryo arrest).Our findings suggest that young patients with POF can experience unpredictable and intermittent spontaneous follicular development, ovulation, and even natural pregnancy. Clinicians should provide appropriate medical guidance and individualized treatments according to fertility requirements, genetic risks and hypoestrogenic symptoms as soon as possible.