Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Front Endocrinol (Lausanne). 2022 Oct 24;13:985525. doi: 10.3389/fendo.2022.985525. eCollection 2022.
Hemoglobinopathies are autosomal recessive disorders that occur when genetic mutations negatively impact the function of hemoglobin. Common hemoglobinopathies that are clinically significant include sickle cell disease, alpha thalassemia, and beta thalassemia. Advancements in disease-modifying and curative treatments for the common hemoglobinopathies over the past thirty years have led to improvements in patient quality of life and longevity for those who are affected. However, the diseases, their treatments and cures pose infertility risks, making fertility preservation counseling and treatment an important part of the contemporary comprehensive patient care. Sickle cell disease negatively impacts both male and female infertility, primarily by testicular failure and decreased ovarian reserve, respectively. Fertility in both males and females with beta thalassemia major are negatively impacted by iron deposition due to chronic blood transfusions. Hematopoietic stem cell transplant (HSCT) is currently the only curative treatment for SCD and transfusion dependent beta thalassemia. Many of the conditioning regimens for HSCT contain chemotherapeutic agents with known gonadotoxicity and whole-body radiation. Although most clinical studies on toxicity and impact of HSCT on long-term health do not evaluate fertility, gonadal failure is common. Male fertility preservation modalities that exist prior to gonadotoxic treatment include sperm banking for pubertal males and testicular cryopreservation for pre-pubertal boys. For female patients, fertility preservation options include oocyte cryopreservation and ovarian tissue cryopreservation. Oocyte cryopreservation requires controlled ovarian hyperstimulation (COH) with ten to fourteen days of intensive monitoring and medication administration. This is feasible once the patient has undergone menarche. Follicular growth is monitored transvaginal or transabdominal ultrasound, and hormone levels are monitored through frequent blood work. Oocytes are then harvested a minimally invasive approach under anesthesia. Complications of COH are more common in patients with hemoglobinopathies. Ovarian hyperstimulation syndrome creates a greater risk to patients with underlying vascular, pulmonary, and renal injury, as they may be less able to tolerate fluids shifts. Thus, it is critical to monitor patients undergoing COH closely with close collaboration between the hematology team and the reproductive endocrinology team. Counseling patients and families about future fertility must take into consideration the patient's disease, treatment history, and planned treatment, acknowledging current knowledge gaps.
血红蛋白病是一种常染色体隐性遗传病，当基因突变对血红蛋白的功能产生负面影响时就会发生。临床上重要的常见血红蛋白病包括镰状细胞病、α 地中海贫血和β 地中海贫血。在过去的三十年中，针对常见血红蛋白病的疾病修饰和治愈治疗取得了进展，改善了受影响患者的生活质量和寿命。然而，这些疾病及其治疗和治愈方法会带来生育风险，因此生育力保存咨询和治疗成为当代综合患者护理的重要组成部分。镰状细胞病对男性和女性的生育能力都有负面影响，主要分别是睾丸衰竭和卵巢储备减少。由于慢性输血，β 地中海贫血重型患者的生育能力也受到铁沉积的影响。造血干细胞移植（HSCT）是目前治疗 SCD 和依赖输血的β 地中海贫血的唯一治愈方法。HSCT 的许多预处理方案都含有已知性腺毒性和全身辐射的化疗药物。尽管大多数关于 HSCT 毒性和对长期健康影响的临床研究不评估生育能力，但性腺功能衰竭很常见。在性腺毒性治疗之前存在的男性生育力保存方式包括青春期男性的精子库和青春期前男孩的睾丸冷冻保存。对于女性患者，生育力保存选择包括卵母细胞冷冻保存和卵巢组织冷冻保存。卵母细胞冷冻保存需要进行控制性卵巢过度刺激（COH），需要进行 10 至 14 天的密集监测和药物管理。一旦患者经历了初潮，这是可行的。通过阴道或腹部超声监测卵泡生长，通过频繁的血液检查监测激素水平。然后在麻醉下通过微创方法采集卵母细胞。血红蛋白病患者的 COH 并发症更为常见。卵巢过度刺激综合征会给有基础血管、肺部和肾脏损伤的患者带来更大的风险，因为他们可能不太能够耐受液体转移。因此，在血液学团队和生殖内分泌学团队之间密切合作的情况下，对接受 COH 的患者进行密切监测至关重要。在为患者及其家属提供关于未来生育能力的咨询时，必须考虑到患者的疾病、治疗史和计划治疗，并承认当前的知识空白。
