Oocyte Cryopreservation and Delayed Pre-Implantation Genetic Diagnosis in the Setting of Erythropoietic Protoporphyria (EPP): A Case Report

Abstract

Fertility preservation (FP) has received considerable focus for cancer patients facing gonadotoxic therapy. A host of patients with hematologic and rheumatologic disorders may also benefit from FP. Porphyria constitutes a spectrum of disorders involving inborn errors of heme synthesis. Erythropoietic protoporphyria (EPP) can vary in severity, and liver and bone marrow transplantation have been recommended in severe cases of EPP.1 In addition numerous hematologic disorders, like EPP, are the result of specific gene disorders and are thus amenable to FP combined with pre-implantation genetic diagnosis (PGD). To describe a case in which fertility preservation was performed in a patient with EPP prior to bone marrow transplant. A 22 year-old G0 presented to a university-based infertility clinic for FP prior to bone marrow transplantation (BMT). Her hematology team had recommended a BMT due to worsening liver function. Genetic testing revealed this patient's EPP resulted from a single allele mutation of ALAS2, making her a heterozygote for X-linked porphyria (XLP). The patient was offered expectant management, ovarian suppression with GnRH agonist, oocyte and embryo banking, and ovarian tissue banking by our FP team. Fertility preservation with oocyte cryopreservation was pursued due to the high risk of post-treatment amenorrhea after bone-marrow transplantation (risk of ovarian failure is 80-100%). Basal ovarian reserve markers were within normal limits (FSH 6.6 mIU/ml with an estradiol of 70 pg/dl; AFC of 15 follicles each side). An antagonist protocol was used for controlled ovarian hyperstimulation, with dosing of 150 units each of recombinant follicle stimulating hormone and human menopausal gonadotropins daily. A peak estradiol of 3771 pg/dl was noted on cycle day 9, and human chorionic gonadotropin 10,000 units was administered on the same day. Oocyte retrieval was performed 36 hours later, and 21 MII oocytes were retrieved and cryopreserved. Preimplantation genetic diagnosis (PGD) is planned when fertility is desired to screen for embryos aff5cted with EPP. Erythropoietic protoporphyria represents one of many disorders that may require bone marrow transplant (BMT). BMT and the associated medications used to control recipient response are strongly associated with subsequent amenorrhea and ovarian failure. Our case highlights the need to discuss fertility preservation with all patients undergoing BMT and the potential to combine fertility preservation with future PGD. 1.Balwani M, Desnick RJ. The porphyrias: advances in diagnosis and treatment. Blood. 2012 Nov;120(23):4496-504.2.Meirow, D, Biederman, H, Anderson, R A, Wallace, W, Hamish B. Toxicity of Chemotherapy and Radiation on Female Reproduction. Clin Obstet Gynecol. 2010 Dec: 53(4): 727-39.3.Jadoul P, Donnez J. How does bone marrow transplantation affect ovarian function and fertility? Curr Opin Obstet Gynecol. 2012.