Hematologic cancers in women: from fertility preservation to post-cancer fertility outcomes.

Abstract

STUDY QUESTION How do hematological characteristics affect ovarian reserve, ovarian response to ovarian stimulation, and fertility outcomes? SUMMARY ANSWER Although lymphoma characteristics impact serum AMH levels, they do not affect, per se, the response to ovarian stimulation and the number of mature oocytes recovered at the time of fertility preservation; in addition, fertility in survivors of hematologic malignancies is relatively conserved. WHAT IS KNOWN ALREADY Hematologic cancers can affect young women of reproductive age. While survival rates have improved over the years due to advances in treatment protocols, the treatments used can impact fertility. Fertility preservation methods, such as oocyte or ovarian tissue cryopreservation, are increasingly offered, but concerns remain about reduced ovarian reserve and response to ovarian stimulation in women with these cancers, which may influence the effectiveness of fertility preservation strategies. Moreover, fertility potential after hematologic cancers has been poorly studied. STUDY DESIGN, SIZE, DURATION This is a retrospective, observational bi-centric cohort study. All patients with hematologic cancer (lymphoma, leukemia, myeloma, and myelodysplastic syndrome) who underwent fertility preservation before gonadotoxic treatment (n = 286) from January 2013 to March 2023 were included. For fertility after cancer, and use of frozen oocytes/embryos, the endpoint date was 7 July 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS Only patients with lymphoma were included for analysis of ovarian reserve (n = 238) and ovarian response to ovarian stimulation (n = 230). Low ovarian reserve and impaired ovarian response to ovarian stimulation were defined as AMH <1.2 ng/ml and ≤9 mature oocytes retrieved after ovarian stimulation, respectively, according to POSEIDON criteria. A Cox regression model was used to determine predictive factors of impaired response to ovarian stimulation, low ovarian reserve, and pregnancy after cancer. Cumulative incidence of pregnancy and cumulative use of frozen oocytes/embryos was calculated in all patients suffering from hematological malignancies. MAIN RESULTS AND THE ROLE OF CHANCE There was an impact of lymphoma characteristics on AMH levels independent of age. After adjustment based on POSEIDON Groups 3 and 4, no specific impact of lymphoma characteristics (e.g. stage, clinical, or biologic B signs) on ovarian response to ovarian stimulation was observed. Regarding post-cancer fertility in the whole population, among the women who tried to conceive, 62% achieved at least one pregnancy, and 85% of these occurred naturally. After adjustment, positive predictive factors for pregnancy were age <35 years, being in a relationship at the first oncofertility consultation, and absence of hematopoietic stem cell transplantation. LIMITATIONS, REASONS FOR CAUTION Limitations include potential biases due to the heterogeneity of hematological conditions and the retrospective design, which may lead to missing data. Additionally, the duration of follow-up may not be sufficient to evaluate long-term fertility outcomes. WIDER IMPLICATIONS OF THE FINDINGS Lymphoma characteristics did not affect the response to ovarian stimulation in terms of mature oocyte retrieval, although AMH levels were impaired. Reassuring post-cancer fertility data support informed decision-making regarding fertility preservation techniques. Larger prospective studies are needed to tailor oncofertility counseling, ensuring optimized care and reproductive outcomes. STUDY FUNDING/COMPETING INTEREST(S) Medical editorial support was provided by Peter Todd of Tajut Ltd (Kaiapoi, New Zealand) and was funded by AFPR (Advances in Fertility Preservation and Reproduction). The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER N/A.