Menstrual cycle characteristics of young females with occult primary ovarian insufficiency at initial diagnosis and one-year follow-up with serum amh level and antral follicle count.

Yilmaz Guzel,Kayhan Yakin,Yilda Arzu Aba,Ozgur Oktem,Samuel Kim

doi:10.1371/journal.pone.0188334

Abstract

Occult primary ovarian insufficiency (also known as incipient ovarian failure or diminished ovarian reserve) is defined as serum AMH level ≤1.1ng/mL in women under age 30. Limited data is available regarding the prevalence of occult POI, the preceding menstrual characteristics and its natural course in otherwise healthy young females. We aimed in this prospective observational study to determine the prevalence of occult POI in young females (< age 30) screened with serum AMH measurement; and analyze the patterns of change in their menstruation at initial assessment and one-year follow-up in relation to the changes in ovarian reserve quantitatively assessed with AMH and AFC. 963 young female college students under age 30 voluntarily participated in this study. 43 of them (4.4%) were diagnosed with occult POI as their AMH levels were ≤ 1.1ng/mL. Thirty-eight (83.4%) of them have regular cycles and denied any menstrual irregularity in the last 12 months. This rate was not statistically different from 7.3% of those with AMH>1.1ng/mL who reported at least one abnormal menstrual cycle in the last year (p = 0.36). Cycle length was significantly shorter in females with AMH ≤ 1.1ng/mL compared to those with AMH>1.1ng/mL (25.1±3.2 vs. 31.2±2.8 respectively, p<0.001). Karyotype, FMR-1 mutation analyses and auto-antibody screening returned normal in all. At one-year follow-up AMH, AFC and mean cycle length were further reduced compared to their values at initial assessment. Now, a greater proportion of the participants with occult POI were menstruating regularly at every 21 days compared to the initial evaluation one year ago (39.5% vs. 13.9% respectively, p = 0.013). Twenty-five underwent oocyte cryopreservation. These findings underscore the importance of screening young females with AMH for possible occult POI. It also emphasizes that young females with critically diminished ovarian reserve may continue to menstruate regularly without any characteristic menstrual abnormality other than shortening of cycle length.

Highlights

Primary ovarian insufficiency (POI) is a condition in which women under the age of 40 experience oligomenorrhea or amenorrhea for 4 months or more, in association with serum follicle stimulating hormone (FSH) levels in the menopausal range on two occasions obtained at least one month apart according to the most recent ESHRE guidelines [1, 2]
Any subfertility problem in these women might be hidden and occult primary ovarian insufficiency (POI) as an underlying cause of it may escape from professional attention and remain undiagnosed until it progresses into more advanced stages of low ovarian function and becomes symptomatic as menstrual abnormality
The mean age, BMI, day of menstrual cycle at the time of blood sampling, and age at menarche were comparable between the participants with and without occult POI (Table 1)

Summary

Introduction

Primary ovarian insufficiency (POI) is a condition in which women under the age of 40 experience oligomenorrhea or amenorrhea for 4 months or more, in association with serum follicle stimulating hormone (FSH) levels in the menopausal range on two occasions obtained at least one month apart according to the most recent ESHRE guidelines [1, 2]. The term POI describes a continuum of impaired ovarian function rather than a specific end point of permanent loss of ovarian function It is less stigmatizing than the other terms premature ovarian failure or premature menopause [4, 5]. The diagnosis of occult POI is problematic as it may develop insidiously without development of oligo/amenorrhea and there is no a proper diagnostic method in its early recognition as mentioned above. This is true for young females who are otherwise healthy, not interested in childbearing and have regular menses. We aimed in this prospective observational study to determine the prevalence of occult POI in young females (< age 30) screened with serum AMH measurement; and analyze the patterns of change in their menstruation at initial assessment and at one-year follow-up in relation to quantitative assessment of ovarian reserve with AMH and AFC

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Discussion

Conclusion