The medical and ethical challenges of fertility preservation in teenage girls: a case series of sickle cell anaemia patients prior to bone marrow transplant

Abstract

Cryopreservation of oocytes has been proposed as a way of storing gametes in young patients at high risk of infertility and premature ovarian failure. Recent advances in cryobiology have yielded promising results, leading to oocyte cryopreservation becoming a mainstay of fertility preservation. In this case series, we describe the feasibility of performing ovarian stimulation, and the ethical challenges faced, in teenage girls, aged 14-18 years, prior to undergoing bone marrow transplant for sickle cell anaemia. All eight consecutive cases completed ovarian stimulation and oocyte retrieval with mature oocytes being found and cryopreserved for each patient. The mean dose of gonadotrophin stimulation was 2134.38 IU (95% CI 1593.34-2675.4) and the mean duration of treatment was 11 days (95% CI 10.02-11.98). The mean number of oocytes retrieved was 14.88 (95% CI 7.39-22.36), of which a mean of 12.13 (95% CI 4.72-19.54) oocytes were mature and cryopreserved. There was one case of moderate ovarian hyperstimulation syndrome that required hospital admission for supportive treatment. Oocyte cryopreservation is a technique that can be successfully employed after the retrieval of mature oocytes from the peripubertal ovary, restoring hope to these patients, and their families, of having their own genetic children in the future.

Desire for parenthood and reproductive health knowledge in adolescents and young adults with sickle cell disease and their caregivers

“…5 Oocyte cryopreservation is more invasive, expensive, and likely higher risk in women with SCD due to hormonal stimulation, though reports of successful cryopreservation in AYA females with SCD prior to hematopoietic stem cell transplantation have been published. 29 Given that hydroxyurea improves clinical outcomes and is being offered to more young children with SCD, 3,4 future studies are needed to establish optimal strategies for ongoing reproductive health counseling for patients with SCD and their caregivers and to examine fertility outcomes in both males and females with SCD on hydroxyurea. These studies will determine if fertility preservation strategies for patients with SCD on hydroxyurea are needed and if existing fertility preservation strategies for both pre-and postpubertal children with SCD should be further tested.…”

Challenges of fertility preservation in non‐oncological diseases

“…However, given the already heavy psychological burden for these young women, with the daily need for injections and regular follow ups (transvaginal ultrasound and hormonal blood test monitoring), then transvaginal oocyte retrieval could be experienced as particularly distressing. Moreover, in 80% of these individuals, the optimal gonadotropin dosage for oocyte harvesting needs to be increased, with a higher risk of developing ovarian hyperstimulation . Finally, the risk of thrombotic or hemorrhagic complications should be thoroughly evaluated before counseling these women, considering their clinical background .…”

“…Finally, the risk of thrombotic or hemorrhagic complications should be thoroughly evaluated before counseling these women, considering their clinical background . Lavery et al reported fewer than 10 mature oocytes collected in 4 out of 8 adolescent girls with sickle cell anemia after COS, limiting the chances of future pregnancy . Oocyte freezing was also proposed in a 13‐year‐old with premenarchal myelodysplastic syndrome.…”

“…22 This strategy requires around 14 days and provides around 8 mature oocytes per cycle to cryopreserve in women with cancer, varying according to the age. [22][23][24] Previous studies showed that vitrified oocytes have a comparable outcome to fresh ones. 1,25 According to guidelines, it is the first option for adult women facing gonadotoxic treatment.…”

Allogeneic stem cell transplantation for sickle cell disease

“…In a separate prospective trial, over half of female recipients of HSCT had diminished ovarian reserve, and only three of 13 males had normal testosterone levels following HSCT, consistent with a diagnosis of hypogonadotropic hypogonadism. [27] Ovarian hyperstimulation and oocyte preservation has been done successfully in SCD patients prior to undergoing HSCT,[28] and sperm cryopreservation is also possible. It is particularly important for physicians to be proactive about discussing fertility preservation including the use of gamete or embryo cryopreservation since many SCD patients are being transplanted at young ages before they are ready to consider child-bearing.…”