Women with Sickle Cell Disease May Have Earlier Decline of Ovarian Function, Study Suggests

Reproductive capacity, specifically the number of eggs left in the ovaries, may decline earlier in women with sickle cell disease (SCD), a study reports. 

Although sickle cell disease patients in this study had no reported fertility problems, they produced less of an ovarian hormone, known as the anti-Müllerian hormone (AMH), thought to be important for the development of eggs.

The decline of AMH started at younger ages in SCD patients, which may mean the capacity of their ovaries to produce mature eggs tends to decline faster.

The study, “Ovarian reserve in women with sickle cell disease,” was published in the journal PLOS ONE.

Based on a number of hints from prior studies, researchers at the Guy’s and St Thomas NHS Trust and King’s College in the U.K. investigated whether SCD affected the ovaries’ function in women of reproductive age.

Their hypothesis was based on several reproductive issues described for men with SCD including fertility and testosterone production problems. However, much less is known about these issues in women with the disease.

One study found a delay in the first menstruation cycle of females with SCD, while other reports argue that iron overload due to repeated blood transfusions, SCD-caused blockage of blood vessels, and a deficiency of oxygen delivery to tissues may impair ovarian function and lead to its premature failure.

Researchers looked at SCD women’s ovarian function by measuring AMH, a surrogate marker of the number of follicles, which are the ovarian structures containing immature eggs, ready to resume development at each menstrual cycle. AMH is a hormone produced by reproductive tissues, including the testicles in males and the ovaries in females.

In women of reproductive age (15 to 49 years old), the more ovarian follicles a woman has, the more AMH her ovaries produce, so the levels of the hormone in the blood can be used to assess how many follicles a woman has left in her ovaries, known as her ovarian reserve.

In this study, a total of 50 SCD female patients were matched with 73 control women without a blood disorder by age, ethnicity, and presence of regular menstrual cycles. 

Participants were 25 to 45 years old. The SCD patients were being seen at the hematology clinic at Guy’s and St Thomas NHS Foundation Trust, and female controls were being followed at the reproductive medicine clinic due to fertility problems.

Results showed that women with SCD produced less AMH and at a younger age than controls. The typical blood levels of AMH for fertile women range from 7 to 28 pmol/l, or 1–4 ng/ml. In SCD patients, serum AMH concentration was 7.6 pmol/l compared with 13.4 pmol/l in women without a blood disorder.

Serum AMH level is known to decline throughout a women’s reproductive years, but the study showed that it declines faster in women with SCD older than 30.

In women ages 36 to 40, 90% of those with SCD had negligible (less than 1.5 pmol/l) or low amounts of AMH (1.5–6.5 pmol/l), compared with 55% in the control group who had low or negligible levels.

“In patients <30 years, there was no significant difference in the prevalence of patients with normal AMH levels in the control and SCD group,” the researchers said. 

Results also suggest that SCD patients are 2.6 times more likely to have low AMH levels than those without SCD.

Accordingly, the proportion of women with high AMH (over 20 pmol/l) was significantly lower in the SCD group (6%) than in the control group (19%).

According to the authors, this is the first study showing that women of reproductive age with SCD have significantly lower AMH levels, “which may be indicative of reduced ovarian reserve when compared to healthy controls.”

Given the current trend in the Western part of the world for not having children until later in life, the researchers advise women with SCD to be aware that their ovaries may age faster and that they may have a relatively shorter reproductive window.

More studies are warranted to understand the full impact of SCD on female reproduction and to see if the severity, the type of SCD mutation, and frequency of acute sickling episodes affect reproduction.