New study links sickle cell anemia to lower ovarian reserve in women

Findings support early fertility counseling for women living with SCA

Written by Andrea Lobo, PhD |

A woman talks to a doctor holding a clipboard.

Women with sickle cell anemia (SCA), the most common and severe form of sickle cell disease (SCD), have significantly lower ovarian reserve relative to women without SCA and with proven fertility, a study in Nigeria shows. Ovarian reserve is a marker-based estimate of the remaining supply of eggs in the ovaries.

While women with SCA also had an altered profile of markers of oxidative stress, an imbalance that can damage cells and could influence that reserve, the researchers found no significant association between the oxidative stress markers measured and ovarian reserve.

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Early fertility counseling may be important for women with SCA

“These findings suggest that other disease-related factors, beyond the oxidative stress indices measured in this study, may contribute to ovarian dysfunction in SCA,” the researchers wrote. “Clinically, our results highlight the importance of early fertility counseling and consideration of fertility preservation strategies in women with [SCA].”

The study, “Ovarian reserve and oxidative stress in sickle cell anaemia: a comparative cross-sectional study,” was published in Scientific Reports.

SCA is caused by the production of a faulty version of hemoglobin, the oxygen-carrying protein in red blood cells. This faulty protein causes red blood cells to take on a sickle-like shape, making them more prone to breaking apart. This can lead to symptoms such as anemia, or a shortage of red blood cells.

Sickle-shaped cells can also block blood flow in small vessels, reducing oxygen delivery to tissues and leading to painful vaso-occlusive crises (VOCs).

In women with SCA, the ovarian reserve, an indicator of female fertility potential, may be compromised due to chronic anemia, VOCs, and oxidative stress. Oxidative stress results from an imbalance between the production of potentially harmful molecules and the body’s ability to neutralize them with antioxidant molecules.

However, “few studies systematically explored ovarian reserve in women with SCA, highlighting the need for research in this area,” the researchers wrote.

To learn more, a team of researchers at Lagos State University, in Nigeria, compared markers of ovarian reserve and oxidative stress in 75 women with SCA in a stable clinical state with those in 75 women without SCA and proven fertility (control group).

Study included women with SCA and women with proven fertility

Participants had a mean age of around 27 years. The largest share of women were under 25 years old (41.3%), followed by ages 30 to 34 (24%), 25 to 29 (22.7%), and 35 and older (12%).

Women with SCA were significantly more likely to be underweight compared with women without SCA (25.3% vs. 1.3%) and to have no children (78.7% vs. 42.7%).

Ovarian reserve was assessed via blood levels of anti-Mullerian hormone (AMH), which reflects the remaining pool of eggs, and antral follicle count (AFC), a count of ovarian follicles seen during an ultrasound exam. Follicles are the ovarian structures that contain immature eggs.

Compared with women without SCA, women with SCA had significantly lower median blood AMH levels (1.52 vs. 3.8 nanograms/mL) and median AFC (12 vs. 15 follicles), consistent with a lower ovarian reserve. The SCA group was also significantly less likely to have high AMH levels than the control group.

Regarding oxidative stress, the median blood levels of the antioxidant enzyme superoxide dismutase were significantly lower in the SCA group (1.5 vs. 2 nanomoles/mL). No significant differences were found in blood levels of glutathione peroxidase, another antioxidant enzyme, and malondialdehyde, a biomarker of oxidative stress.

“This study provides evidence of diminished ovarian reserve in women with HbSS, alongside alterations in selected oxidative stress parameters,” the researchers wrote.

Age predicted ovarian reserve among women with SCA

Lower AMH levels and a lower AFC were each significantly associated with older age. However, no significant links were observed between these markers of ovarian reserve and the measured oxidative stress markers or blood hemoglobin levels.

“Thus, although [SCA] women had significantly altered oxidative stress profiles compared with controls, these differences were not correlated with ovarian reserve markers,” the researchers wrote.

Further statistical analysis identified age as the only predictor of ovarian reserve in women with SCA. Specifically, increasing age was significantly associated with lower AMH and AFC.

“The absence of significant correlations between oxidative stress markers and ovarian reserve should be interpreted cautiously, as it may reflect the limited panel of biomarkers assessed, or compensatory physiological mechanisms rather than a lack of biological effect,” the team wrote. “Oxidative stress might contribute indirectly, possibly through cumulative tissue damage or interactions with other factors, which require further investigation.”