Reproductive characteristics of women diagnosed with premature ovarian insufficiency

Abstract

In this retrospective cohort study (n = 479), the proportion of women with premature ovarian insufficiency (POI) who conceived was assessed, the reproductive characteristics of women with POI who had previously been pregnant or had never been pregnant compared, and the interval between last conception and the menopause in women with POI who had become pregnant assessed. Time to pregnancy and maternal age at first childbirth were compared between women with POI and population-based controls (n = 2304). Women with POI who had previously been pregnant (n = 249 [52%]) experienced menopause at a later age compared with controls (35.0 years: interquartile range [IQR] 32.0–37.5 versus 30.0 years [IQR 23.0–35.0]; P < 0.001). The median interval between last conception and menopause in the former group was 4.0 years (IQR 1.0–8.0). Time to pregnancy did not differ between women with POI and controls. Women with POI were younger at first childbirth compared with controls (27.3 years [IQR 23.4–30.5] versus 29.2 years [26.4–32.0]; P < 0.001). The reproductive capacity of young women with POI is comparable to women in the general population, up until a given age; thereafter a rapid loss of the potential to conceive occurs.

Introduction

Women with premature ovarian insufficiency (POI) experience menopause before 40 years of age (Coulam et al., 1986) This condition affects about 1% of women, and is associated with multiple health problems, such as infertility, osteoporosis, cardiovascular disease and decreased well-being (Roeters van Lennep et al, 2014, Uygur et al, 2005, van der Stege et al, 2008). It is considered a multifactorial, heterogeneous condition, for which the exact underlying cause remains unclear in most affected women (Bachelot et al., 2009) Various genetic causes have been identified, and associations with autoimmune diseases and environmental factors, such as smoking, have been described (Hoek et al, 1997, van Asselt et al, 2004, Voorhuis et al, 2014).

Extremely low success rates have been reported with various infertility interventions in women with POI (De Vos et al, 2010, Hsueh et al, 2015). To date, little information is available concerning the reproductive characteristics of women diagnosed with POI during their preceding reproductive life (Bachelot et al, 2009, Janse et al, 2010).

On the basis of data from general population studies, it is thought that, for a given woman, a fixed time interval exists between the various reproductive phases, i.e. the onset of subfertility, infertility and the subsequent age at menopause (Broekmans et al, 2009, te Velde, Pearson, 2002). Menopause generally occurs around the age of 51 years, with an age range extending between 40 and 60 years (Treloar et al., 1967). Historical studies carried out in populations with unrestricted reproduction show a mean age at last childbirth of 41 years, suggesting that the end of natural fertility occurs about a decade before natural menopause (Menken et al, 1986, Wood, 1989). If decreasing reproductive capacity with advancing age in women is indeed caused by a gradual decrease in both the quantity and quality of the oocytes, it is plausible that an early age at menopause is preceded by an early age at infertility (Broekmans et al., 2009).

Whether the above mentioned association between fertility loss and age at menopause is similar in women diagnosed with POI is unknown. Therefore, the present descriptive study aimed to illustrate the reproductive characteristics in a large cohort of well-phenotyped women with POI. Of particularly focus was the proportion of women with POI who were able to conceive, with analysis of the following: possible differences between women with POI who had previously been pregnant or those who had never been pregnant; the interval between last conception and menopause in women with POI who had achieved a pregnancy; and its possible association with spontaneous miscarriage. Finally, potential differences in the required time to establish a pregnancy and age at first childbirth were compared between women with POI and controls from a general fertile population.