Fertility Preservation Considerations in Female Patients with Benign and Malignant Hematologic Disease

Female patients of reproductive age with cancer often require treatment that can compromise their future fertility. Treatment-related infertility is an important cancer survivorship issue and is associated with depression and diminished quality of life. Recent advances in reproductive health care provide the opportunity to preserve fertility prior to the initiation of cancer therapy. Clinical guidelines recommend that oncology providers counsel patients about the risk of treatment-related infertility and fertility preservation options, and that they refer those who are interested in fertility preservation to fertility specialists. Guidelines endorse the use of assisted reproductive techniques (ART) provided by reproductive endocrinologists to preserve fertility in young female patients with cancer. In addition, ovarian suppression with gonadotropin-releasing hormone (GnRH) agonists may be considered for ovarian protection during chemotherapy. This article reviews currently available and emerging ART for fertility preservation in female patients of reproductive age with cancer and current data supporting the use of ovarian suppression for ovarian protection during chemotherapy in this population. We also review the uptake of fertility services and discuss barriers to fertility preservation in female patients of reproductive age with cancer.

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Combining fertility preservation procedures to spread the eggs across different baskets: a feasibility study

Human Reproduction ◽

10.1093/humrep/deaa193 ◽

2020 ◽

Vol 35 (11) ◽

pp. 2524-2536 ◽

Cited By ~ 1

Author(s):

S Delattre ◽

I Segers ◽

E Van Moer ◽

P Drakopoulos ◽

I Mateizel ◽

...

Keyword(s):

Fertility Preservation ◽

Ovarian Stimulation ◽

Ovarian Function ◽

Ex Vivo ◽

Ovarian Tissue ◽

Ovarian Tissue Cryopreservation ◽

Reproductive Outcomes ◽

Female Patients ◽

Clinical Scenarios

Abstract STUDY QUESTION What is the reproductive potential following combinations of ovarian stimulation, IVM and ovarian tissue cryopreservation (OTC) in female patients seeking fertility preservation (FP)? SUMMARY ANSWER In selected patients, combining different FP procedures is a feasible approach and reproductive outcomes after FP in patients who return to attempt pregnancy are promising. WHAT IS KNOWN ALREADY FP is increasingly performed in fertility clinics but an algorithm to select the most suitable FP procedure according to patient characteristics and available timeframe is currently lacking. Vitrification of mature oocytes (OV) and OTC are most commonly performed, although in some clinical scenarios a combination of procedures including IVM, to spread the sources of gametes, may be considered in order to enhance reproductive options for the future. STUDY DESIGN, SIZE, DURATION Retrospective, observational study in a university-based, tertiary fertility centre involving all female patients who underwent urgent medical FP between January 2012 and December 2018. Descriptive analysis of various FP procedures, either stand-alone or combined, was performed, and reproductive outcomes of patients who attempted pregnancy in the follow-up period were recorded. PARTICIPANTS/MATERIALS, SETTING, METHODS In total, 207 patients underwent medical FP. Patient-tailored strategies and procedures were selected after multidisciplinary discussion. When deemed feasible, FP procedures were combined to cryopreserve different types of reproductive tissue for future use. The main primary outcome measure was the number of mature oocytes. Live birth rates were evaluated in patients who returned for reproductive treatment. MAIN RESULTS AND THE ROLE OF CHANCE Among patients seeking FP, 95/207 (46%) had breast cancer, 43/207 (21%) had haematological malignancies and 31/207 (15%) had a gynaecological tumour. Mean ± SD age was 27.0 ± 8.3 years. Eighty-five (41.1%) patients underwent controlled ovarian stimulation (COS), resulting in 10.8 ± 7.1 metaphase II (MII) oocytes for vitrification. Eleven (5.3%) patients had multiple COS cycles. Transvaginal oocyte retrieval for IVM was performed in 17 (8.2%) patients, yielding 9.2 ± 10.1 MII oocytes. Thirty-four (16.4%) patients underwent OTC combined with IVM of oocytes retrieved from ovarian tissue ‘ex vivo’ (OTO-IVM), yielding 4.0 ± 4.3 MII oocytes in addition to ovarian fragments. Seventeen (8.2%) patients had OTC combined with OTO-IVM and transvaginal retrieval of oocytes for IVM from the contralateral ovary, resulting in 13.5 ± 9.7 MII oocytes. In 13 (6.3%) patients, OTC with OTO-IVM was followed by controlled stimulation of the contralateral ovary, yielding 11.3 ± 6.6 MII oocytes in total. During the timeframe of the study, 31/207 (15%) patients have returned to the fertility clinic with a desire for pregnancy. Of those, 12 (38.7%) patients had preserved ovarian function and underwent ART treatment with fresh oocytes, resulting in nine (75%) livebirth. The remaining 19 (61.3%) patients requested warming of their cryopreserved material because of ovarian insufficiency. Of those, eight (42.1%) patients had a livebirth, of whom three after OTO-IVM. To date, 5/207 patients (2.4%) achieved an ongoing pregnancy or livebirth after spontaneous conception. LIMITATIONS, REASONS FOR CAUTION Our FP programme is based on a patient-tailored approach rather than based on an efficiency-driven algorithm. The data presented are descriptive, which precludes firm conclusions. WIDER IMPLICATIONS OF THE FINDINGS Combining different FP procedures is likely to enhance the reproductive fitness of patients undergoing gonadotoxic treatment but further follow-up studies are needed to confirm this. STUDY FUNDING/COMPETING INTEREST(S) No external funding was used for this study and the authors have no competing interests. TRIAL REGISTRATION NUMBER N/A.

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Concept Paper on the Technique of Cryopreservation, Removal and Transplantation of Ovarian Tissue for Fertility Preservation

Geburtshilfe und Frauenheilkunde ◽

10.1055/a-0664-8619 ◽

2018 ◽

Vol 79 (01) ◽

pp. 53-62 ◽

Cited By ~ 13

Author(s):

Matthias Beckmann ◽

Laura Lotz ◽

Bettina Toth ◽

Dunja Baston-Büst ◽

Tanja Fehm ◽

...

Keyword(s):

Surgical Technique ◽

Fertility Preservation ◽

Reproductive Medicine ◽

Birth Rate ◽

Ovarian Tissue ◽

Established Method ◽

Female Patients ◽

Oncological Therapy ◽

German Speaking ◽

Fertility Protection

AbstractThe cryopreservation of ovarian tissue with subsequent transplantation of the tissue represents an established method of fertility protection for female patients who have to undergo gonadotoxic therapy. The procedure can be performed at any point in the cycle and thus generally does not lead to any delay in oncological therapy. With the aid of this procedure, more than 130 births to date worldwide have been able to be recorded. The birth rate is currently approximately 30% and it can be assumed that this will increase through the further optimisation of the cryopreservation and surgical technique. The concept paper presented here is intended to provide guidance for managing cryopreservation and transplantation of ovarian tissue to German-speaking reproductive medicine centres.

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Fertility in Female Patients After Allogeneic Stem Cell Transplantation Following Reduced-Intensity Conditioning (RIC allo-SCT)

Blood ◽

10.1182/blood.v118.21.3057.3057 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3057-3057

Author(s):

Emmanuelle Assouline ◽

Roberto Crocchiolo ◽

Thomas Prebet ◽

Sabine Furst ◽

Jean El-Cheikh ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Fertility Preservation ◽

Allogeneic Stem Cell Transplantation ◽

Hematological Malignancy ◽

Reduced Intensity Conditioning ◽

Female Patients ◽

Biological Criteria ◽

Reduced Intensity

Abstract Abstract 3057 Objective There is only limited data available on women's fertility for younger patients treated by reduced intensity conditioning allogeneic stem cell transplantation (RIC allo-SCT). This issue is important as RIC allo-SCT is a potential curative treatment and as women's fertility preservation methods had improved with now several births after ovarian cryoconservation for example. Materials and Methods We evaluate fertility among female patients younger than 35 years old receiving RIC allo-SCT for hematological malignancy or aplastic anemia. This is a single center retrospective study. Informations on therapies before RIC allo-SCT were collected including disease characteristics, previous therapy (chemo, radiotherapy, autologous SCT), and allogeneic transplantation modalities. Data on fertility evaluation after RIC allo-SCT included clinical and biological criteria (see below). Any proposed option of fertility preservation was analyzed as well as any information about potential loss of fertility and/or ovarian failure received by patients before RIC allo-SCT. Results Ninety-six patients under the age of 35 underwent RIC allo-SCT between January 2000 and January 2010. Fifty patients are alive at last follow-up, 23 of them are female patients. Twenty-two patients were available for the study. Mean age at last follow-up is 32 (22–46), mean age at diagnosis is 27 (17–35). Median follow-up after RIC allo-SCT is 47 months. Diagnoses were: Hodgkin's lymphoma (36, 4%), Acute myeloid leukemia (22, 7%), aplastic anaemia (13, 6%), Acute lymphoblastic leukemia (9%), multiple myelome (9%), non-Hodgkin's lymphoma (4, 5%), Chronic lymphocytic leukemia (4, 5%). The median number of previous treatment regimen before allo was × (1 line (36.9%), 2 (41%), 3 (9%)). One patient received sub-diaphragmatic radiotherapy at dose of 36Gy and three patients received RIC allo-SCT without prior chemotherapy (AA cases). ASCT followed BEAM or high-dose Melphalan conditioning in 45, 4% of patients. RIC allo-SCT was realized after the following conditioning regimens: cyclophosphamide-ATG (13, 6%), fludarabine-busulfan-ATG (45, 4%), TBI 2Gy +/− Fludarabine + /- Cyclophosphamide (40, 9%). Before RIC allo-SCT 86, 3% of patients had regular menses and 50, 9% had previous pregnancies (1–3). After RIC allo-SCT, amenorrea affects 68% of patients, 87% of whom have menopausal symptoms. All three AA patients have regular cycles and became pregnant after RIC allo-SCT whereas none of the patient treated for hematological malignancy became pregnant. Biological hormonal evaluation showed impaired ovarian function for 82% of the patients with elevated LH and FSH values and low Oestradiol and Anti Mullerian Hormon values. On a more general aspect, Only six (27, 2%) patients declared to have been correctly informed before RIC allo-SCT on potential deleterious effects on fertility by anticancer treatment; five (22, 7%) patients declared to have been partially informed and 11 (50%) not informed at all, respectively. Fertility preservation was proposed to five patients before RIC allo-SCT: 2 refused, 2 had in vitro fecundation and 1 had ovarian cryopreservation. Conclusion This is the first study specifically focusing on fertility after RIC allo-SCT among young female patients. Results show a high rate of ovarian failure, evaluated by both clinical and biological criteria. The significant difference here between AA and malignant diseases suggests that a potential deleterious role was played by previous anticancer treatments including HD chemotherapy followed by auto SCT rather than by RIC allo-SCT itself. Disclosures: No relevant conflicts of interest to declare.

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Increasing fertility preservation counseling prior to chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.27_suppl.225 ◽

2019 ◽

Vol 37 (27_suppl) ◽

pp. 225-225

Author(s):

Candice Schwartz ◽

Ari Seifter ◽

Ivy Abraham ◽

Caitlin Lopes ◽

Emily Woo ◽

...

Keyword(s):

Fertility Preservation ◽

Medical Center ◽

Insurance Coverage ◽

Academic Medical Center ◽

Post Intervention ◽

Female Patients ◽

Academic Medical ◽

Survey Results ◽

Prohibitive Cost ◽

Common Barriers

225 Background: The 2018 ASCO Guidelines recommend that physicians document discussions about fertility with all female patients < 49 years old at the time of cancer diagnosis. Patients interested in fertility preservation (FP) should be referred to Reproductive Endocrinology and Infertility (REI) prior to chemotherapy. Retrospective review of oncology patients at our academic medical center over 6 months found that 33% of females < 49 years old had FP discussion documented. We aimed to increase FP discussions and help expedite referrals to REI from 33% to 75% within 5 months. Methods: All new chemotherapy orders were reviewed weekly. Female patients between ages 18-49 were identified and charts were abstracted for the following: age, race, diagnosis, stage, type and line of chemotherapy, and FP discussion. If FP was not discussed, the physician was contacted in real time via email to address FP with the patient and document the discussion. Charts were reviewed 2-4 weeks later to determine if FP was documented. To better understand barriers to FP documentation, fellows and attendings were surveyed to target future interventions. Results: From Dec. 2018 to Apr. 2019, 6/27 (22%) patients had documented discussions of FP. Post intervention, this number increased to 17/27 (63%) with one referral to REI. Intent of chemotherapy was curative in 56% of patients, and 67% were receiving their first line of chemotherapy. 2/15 (13%) patients receiving curative treatment and 4/12 (33%) patients receiving palliative chemotherapy had documentation of FP, both of which increased with intervention to 8/15 (53%) and 9/12 (75%), respectively. Conclusions: Our intervention successfully increased FP discussion from 33% to 63%, but we did not meet our goal of 75%. Per our survey results, the most common barriers to FP discussion were time constraints, inexperience discussing FP, and perception of prohibitive cost to the patient. We are designing our next intervention to address provider inexperience with FP discussion. This will include education regarding the financial aspects of REI and discussion of the new Oncofertility law in Illinois (HB2617), which ensures insurance coverage for oncofertility as of Jan 2019.

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