The following article features coverage from the American Society of Hematology 2020 meeting. Click here to read more of Hematology Advisor‘s conference coverage.

Diminished ovarian reserve may be linked to hydroxyurea exposure in girls and women with sickle cell anemia (SCA), and anti-Müllerian hormone (AMH) may serve as a useful marker for ovarian reserve in SCA, according to results of a pilot study presented by Lydia H. Pecker, MD, from the Johns Hopkins University School of Medicine in Baltimore, Maryland, at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.

The results of a previous multicenter study of hydroxyurea and AMH levels suggested “that median [AMH] levels in women with sickle cell anemia are lower than those in the control subjects, and also that diminished ovarian reserve occurs starting in very young women with sickle cell anemia,” said Dr Pecker.2,3  “These findings raised questions about the extent to which disease complications or hydroxyurea affect ovarian reserve,” Dr Pecker continued.


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Dr Pecker and colleagues hypothesized that young women with SCA have lower levels of AMH compared with age- and race-matched controls, and that exposure to hydroxyurea puts these women at increased risk for diminished ovarian reserve (AMH <1.1 ng/mL ± follicle-stimulating hormone [FSH] >10-40 international units [IU]).

Ovarian reserve was measured in adult women with SCA undergoing treatment at the Johns Hopkin’s Adult Sickle Cell Center. Serum levels of ferritin, AMH, FSH, and estradiol were obtained, and ultrasound-based antral follicle count (AFC) was measured. Demographic, reproductive, and SCA histories were collected from each patient, including hydroxyurea exposure and use, and markers of adherence.

In the analysis, AMH levels in women with SCA aged 19 to 25 years and 26 to 31 years were compared with AMH levels in control groups of age-matched Black/African American women with tubal factor infertility and no chemotherapy exposure, and with age-matched levels from a historic cohort from the Multicenter Study of Hydroxyurea (MSH).3 Patient variables were assessed for associations with diminished ovarian reserve or primary ovarian insufficiency (AMH <1.1 ng/mL and FSH ≥40 IU).

The pilot study included 16 women with SCA with a median age of 25.5 years (interquartile range [IQR], 21-29), hemoglobin of 8.8 g/dL (IQR, 8.0-9.2), mean corpuscular volume (MCV) of 96.9 fL (IQR, 88.6-101.1), absolute neutrophil count of 5.7 K/μL (IQR, 3.4-8.4), and ferritin 857 ng/mL (IQR, 246-1957).

All women had been exposed to hydroxyurea, with median age at first exposure of 17.5 years (IQR, 14.5-21) and median time of exposure of 23 months (IQR, 2.8-38.5). Most of the women (12/16, 75%) were taking hydroxyurea during the study visit.

As expected, patients who were older had lower AMH and AFC, and for both age groups, AMH was lower in study participant compared with controls (aged 19-25 years, 2.48 ng/mL vs 7.45 ng/mL; P <.001; aged 26-31 years, 1.34 ng/mL vs 2.04 ng/mL; P =.08).

No significant differences in AMH or AFC were observed between the pilot study cohort and the historical MSH cohort. However, the women aged 19 to 25 years trended toward higher median AFC compared with women aged 26 to 31 years (14 follicles [IQR, 8-35] vs 9 follicles [IQR, 7-12], respectively).

In the pilot study, 25% (4/16) of women, all of whom were taking hydroxyurea and were older than 25 years of age, had diminished ovarian reserve. Approximately one-half (52%) of the women in the MSH cohort and 25% of girls and women (aged, 10-21 years) from a cohort study conducted at Emory University, in Atlanta, Georgia, also demonstrated diminished ovarian reserve in the setting of hydroxyurea exposure.3

Diminished ovarian reserve was associated with lower median AFC (AFC, 5.5 vs 12 oocytes; P =.04) and higher MCV (112 vs 92 fL, P =.02). No differences in patient variables were identified between patients with or without diminished ovarian reserve.

“We conclude that young women with sickle cell anemia have lower ovarian reserve than matched controls,” said Dr Pecker. “This will have implications for informed consent and shared decision making regarding treatment choices, family planning, and fertility preservation for young women with sickle cell disease.”

Limitations of this study include the small sample size and the inability of AMH to predict pregnancy in women without SCA and infertility.

Disclosure: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

Read more of Hematology Advisor’s coverage of the ASH 2020 meeting by visiting the conference page.

References

  1. Pecker LH, Hussain S, Mahesh J, et al. Hydroxyurea is a potential risk factor for diminished ovarian reserve in young adults with sickle cell anemia. Presented at: American Society of Hematology (ASH) 62nd Annual Meeting and Exposition; December 5-8, 2020. Abstract 15.
  2. Pecker LH, Hussain S, Christianson MS, Lanzkron S. Hydroxycarbamide exposure and ovarian reserve in women with sickle cell disease in the Multicenter Study of Hydroxycarbamide. Br J Haematol. 2020;191(5):880-887. doi:10.1111/bjh.16976
  3. Elchuri SV, Williamson RS, Clark Brown R, et al. The effects of hydroxyurea and bone marrow transplant on anti-Müllerian hormone (AMH) levels in females with sickle cell anemia. Blood Cells Mol Dis. 2015;55(1):56-61. doi: 10.1016/j.bcmd.2015.03.012