(94) Ovarian Tissue Cryopreservation in a Patient with Blepharophimosis Ptosis Epicanthus Inversus Syndrome (BPES)

Background: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES; OMIM: 110100) is an autosomal dominant condition characterized by a complex eyelid abnormality, including blepharophimosis, ptosis, epicanthus inversus, and telecanthus. BPES is caused by pathogenic variants in the single-exon gene FOXL2. FOXL2, a forkhead-containing transcription factor, plays an important role in granulosa cell physiology and ovarian development, and has been implicated in various genetic etiologies of premature ovarian insufficiency (POI). There are two BPES types: Type 1, which encompasses premature ovarian insufficiency alongside the above-described eye abnormalities, and Type 2, solely involving eye manifestations. Limited data exist on ovarian histology and function in individuals with FOXL2 mutations but ovarian tissue cryopreservation (OTC) has been advocated in these individuals for fertility preservation.

Case: We describe a case report of a 20-year-old female diagnosed with BPES at the age of 11, attributed to a FOXL2 pathogenic variant (c.827dupG; p.Leu277ProfsTer257). She exhibited irregular menses and diminished ovarian reserve (see Table 1). She attempted oocyte cryopreservation twice; the first attempt was terminated due to a poor response but she was noted to have an antral follicle count (AFC) of 21. With the second cycle her AFC was 19, but resulted in premature ovulation with no oocytes retrieved. Consequently, she underwent OTC via laparoscopic right oophorectomy, revealing ovarian tissue containing multiple follicles, and a decreased follicle density of 11.4 follicles/mm2. (Figure 1, Table 2).

Comments: We present the first reported case of ovarian tissue cryopreservation in a BPES patient. Although FOXL2's role in ovarian development and granulosa cell physiology is well-described, there remains a scarcity of data concerning the effectiveness of oocyte and ovarian tissue cryopreservation for preserving fertility in BPES patients. Further investigation is warranted to unravel the impact of FOXL2 pathogenic variants on folliculogenesis and ovarian function. Such insights are pivotal in the quest for interventions like ovarian tissue cryopreservation and transplantation.