Risk of ovarian hyperstimulation syndrome in women with malignancies undergoing treatment with long-acting gonadotropin-releasing hormone agonist after controlled ovarian hyperstimulation for fertility preservation: a systematic review

Abstract

Background: Fertility preservation is an important quality of life issue for women of reproductive age undergoing gonadotoxic treatment. The possibility of administering an adjuvant long-acting gonadotropin-releasing hormone agonist (GnRHa) with the aim of reducing the number of follicles susceptible to the effects of chemotherapy and thus reducing the risk of ovarian damage is considered in some international society guidelines, particularly in certain cancers such as breast cancer. Nowadays, the administration of long-acting GnRHa after controlled ovarian hyperstimulation (COH) for fertility preservation by cryopreservation of oocytes or embryos is increasingly used. However, cases of ovarian hyperstimulation syndrome (OHSS) have been reported following the use of long-acting GnRHa after COH for fertility preservation, indicating that the potential adverse effects of this treatment need to be further investigated. Objectives: The aim of this systematic review was to comprehensively characterize patients who developed OHSS after treatment with long-acting GnRHa following COH for fertility preservation. Methods: A comprehensive search of major electronic databases through January 2023 was performed. Studies reporting the use of long-acting GnRHa after COH for fertility preservation and the development of OHSS were included. Risk of bias was assessed using a modified version of the Newcastle-Ottawa scale. Results were synthesized qualitatively. Results: Three studies with five patients met the eligibility criteria. The majority of patients were diagnosed with breast cancer and all patients underwent COH for oocyte cryopreservation. OHSS occurred in all patients after administration of long-acting GnRHa. The interval between ovulation induction and administration of long-acting GnRHa thereafter ranged from 3 to 5 days. All patients were treated conservatively and recovered without complications. Conclusion: Current evidence suggests that the use of long-acting GnRHa after COH for fertility preservation may be associated with OHSS. Healthcare providers should thoroughly discuss the benefits and risks of this intervention with their patients before making a decision. Further studies are needed to fully elucidate the causal relationship between long-acting GnRHa and OHSS in this population.

Feasibility and safety of combined laparoscopic and transvaginal oocyte retrieval in a woman with vaginal recurrence of cervical adenocarcinoma: a case report

“…Therefore, strategies such as starting the stimulation cycle in the luteal phase have been proposed to achieve this goal ( 12 ), with recent study demonstrating comparable number of mature oocytes and embryos cryopreserved when compared to standard-start-controlled ovarian stimulation ( 13 ). In addition, the use of a GnRH agonist to induce ovulation has been shown to reduce the risk of ovarian hyperstimulation syndrome ( 14 , 15 ). Co-administration of letrozole has been shown to significantly lower serum estradiol levels compared with conventional ovarian stimulation protocols, making treatment safer ( 16 ).…”

Fertility Preservation and Ovarian Hyperstimulation Syndrome Management in Cancer Care: A Pathophysiological Perspective on Gonadotropin-Releasing Hormone Agonists and Antagonists

“…Although still considered experimental, physicians are increasingly using combined strategies for fertility preservation, such as the administration of a long-acting GnRH agonist after COS for fertility preservation by oocyte and/or embryo cryopreservation. However, this approach has been associated with the occurrence of OHSS [ 5 , 6 ]. The mechanism is a sustained increase in gonadotropins after treatment, which stimulates luteinizing hormone (LH) receptors in the ovaries and leads to an overproduction of angiogenic factors, eventually resulting in OHSS ( Figure 1 ).…”

“…This increase in angiogenic factors increases vascular permeability, leading to fluid accumulation in the abdominal cavity and other areas, along with hemoconcentration, hypercoagulability and electrolyte disturbances, the characteristic features of OHSS. Adapted from Ingold et al [ 5 ].…”

“…In this context, the administration of long-term gonadotropin-releasing hormone (GnRH) agonists is frequently observed in women who have undergone oocyte retrieval for oocyte and/or embryo cryopreservation. However, there are reports of OHSS in women who have undergone COS followed by treatment with long-term GnRH agonists [ 5 , 6 ], despite having no other identifiable risk factors for this complication. A comprehensive understanding of both the pathophysiology of OHSS and the various fertility preservation techniques is crucial, especially for oncology patients.…”