Review Article
Volume 9 Issue 3 - 2020
Future Fertility of Women Cancer Survivors: The Progress in Fertility Preservation
Amanda Farrugia* and Jean Calleja Agius
Department of Anatomy, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
*Corresponding Author: Amanda Farrugia, Department of Anatomy, Faculty of Medicine and Surgery, University of Malta, Msida, Malta.
Received: February 08, 2020; Published: February 26, 2020


Diminished ovarian reserve (DOR) has devastating implications for the affected female in terms of quality of life, fertility, fecundity and overall well-being. DOR can be exacerbated by the use of chemotherapy and gynaecological surgeries. Analysis of the gonadotoxicity and efficacy of chemotherapeutic regimens currently available and the techniques for gynaecological surgeries, allows for the most appropriate regimen or technique to be selected following a risk-benefit ratio analysis. This should be done in conjunction with fertility preservation strategies including cryopreservation, ovarian transposition and suppression, and pharmacological agents. New approaches using fertoprotective agents need to be evaluated in order to keep up with the demand for oncofertility. This ensures the least possible damage to the ovarian environment and the utmost preservation of the follicular pool.

Keywords: Oncofertility; Fertility Preservation; Women; Chemotherapy; Ovarian Cancer; Follicular Pool


  1. Lambertini M., et al. “Cancer and fertility preservation: international recommendations from an expert meeting”. BMC Medicine 14.1 (2016).
  2. Wallace WH., et al. “Fertility preservation in pre-pubertal girls with cancer: the role of ovarian tissue cryopreservation”. Fertility and Sterility 105.1 (2016): 6-12. 
  3. Ben-Aharon I., et al. “Optimizing the process of fertility preservation in pediatric female cancer patients - a multidisciplinary program”. BMC Cancer 16.1 (2016): 620. 
  4. Harada M and Osuga Y. “Where are oncofertility and fertility preservation treatments heading in 2016?” Future Oncology 12.19 (2016): 2313-2321. 
  5. Donnez J and Dolmans MM. “Ovarian cortex transplantation: 60 reported live births brings the success and worldwide expansion of the technique towards routine clinical practice”. Journal of Assisted Reproduction and Genetics 32.8 (2015): 1167-1170. 
  6. Jadoul P., et al. “Efficacy of ovarian tissue cryopreservation for fertility preservation: lessons learned from 545 cases”. Human Reproduction 32.5 (2017): 1046-1054. 
  7. Donnez J and Dolmans MM. “Fertility preservation in women”. Nature Reviews Endocrinology 9.12 (2013): 735-749. 
  8. Anderson RA., et al. “Cancer treatment and gonadal function: experimental and established strategies for fertility preservation in children and young adults”. Lancet Diabetes Endocrinology 3.7 (2015): 56-567. 
  9. Johnson EK., et al. “Fertility Preservation for Pediatric Patients: Current State and Future Possibilities”. Journal of Urology 198.1 (2017): 189-194. 
  10. Massarotti C., et al. “State of the art on oocyte cryopreservation in female cancer patients: a critical review of the literature”. Cancer Treatment Review 57 (2017): 50-57. 
  11. Shenfield F., et al. “Oocyte and ovarian tissue cryopreservation in European countries: statutory background, practice, storage and use”. Human Reproduction 2017.1 (2017). 
  12. Cobo A., et al. “Use of cryo-banked oocytes in an ovum donation programme: a prospective, randomized, controlled, clinical trial”. Human Reproduction 25.9 (2010): 2239-2246. 
  13. Cobo A and Diaz C. “Clinical application of oocyte vitrification: a systematic review and meta-analysis of randomized controlled trials”. Fertility and Sterility 96.2 (2011): 277-285. 
  14. Cobo A., et al. “Is vitrification of oocytes useful for fertility preservation for age-related fertility decline and in cancer patients?”. Fertility and Sterility 99.6 (2013): 1485-1495. 
  15. Rienzi L., et al. “Oocyte, embryo and blastocyst cryopreservation in ART: systematic review and meta-analysis comparing slow-freezing versus vitrification to produce evidence for the development of global guidance”. Human Reproduction Update 23.2 (2017): 139-155. 
  16. Levi Setti PE., et al. “Human oocyte cryopreservation with slow freezing versus vitrification. Results from the National Italian Registry data, 2007-2011”. Fertility and Sterility 102.1 (2014): 90-95. 
  17. Cobo A., et al. “Obstetric and perinatal outcome of babies born from vitrified oocytes”. Fertility and Sterility 102.4 (2014): 1006-1015. 
  18. Patel B and Rossi BV. “Preserving fertility in young patients with lymphoma: an overview”. Blood and Lymphatic Cancer 5 (2014): 1-15. 
  19. Soares M., et al. “Eliminating malignant cells from cryopreserved ovarian tissue is possible in leukaemia patients”. British Journal of Haematology 178.2 (2017): 231-239. 
  20. Donnez J., et al. “Restoration of ovarian activity and pregnancy after transplantation of cryopreserved ovarian tissue: a review of 60 cases of reimplantation”. Fertility and Sterility 99.6 (2013): 1503-1513. 
  21. Kopeika J., et al. “The effect of cryopreservation on the genome of gametes and embryos: principles of cryobiology and critical appraisal of the evidence”. Human Reproduction Update 212 (2015): 209-227. 
  22. Liu M., et al. “Assessment of clinical application of preimplantation genetic screening on cryopreserved human blastocysts”. Reproductive Biology and Endocrinology 14.1 (2016): 16. 
  23. Deng A and Wang W. “Assessment of aneuploidy formation in human blastocysts resulting from cryopreserved donor eggs”. Molecular Cytogenetics 8 (2015): 12. 
  24. Goldman KN., et al. “Long-term cryopreservation of human oocytes does not increase embryonic aneuploidy”. Fertility and Sterility 103.3 (2015): 662–668. 
  25. Liu M., et al. “A modified vitrification method reduces spindle and chromosome abnormalities”. Systems Biology in Reproductive Medicine 2017/05/04 63.3 (2017): 199-205. 
  26. Roness H., et al. “Prevention of chemotherapy-induced ovarian damage”. Fertility and Sterility 105.1 (2016): 20-29. 
  27. Gui T., et al. “Protective effect of gonadotropin-releasing hormone analog on the ovarian reserve in rats receiving cyclophosphamide treatment”. OncoTargets and Therapy 8 (2015): 661-667. 
  28. Oktay K. “Fertility Preservation in Cancer Patients”. Oncology Times 39.4 (2017): 1.8-9. 
  29. Blumenfeld Z., et al. “An ounce of prevention is worth a pound of cure': the case for and against GnRH-agonist for fertility preservation”. Annals of Oncology 25.9 (2014): 1719-1728. 
  30. Taylan E and Oktay K. “Current state and controversies in fertility preservation in women with breast cancer”. World Journal of Clinical Oncology 8.3 (2017): 241-248. 
  31. Leonard RCF., et al. “GnRH agonist for protection against ovarian toxicity during chemotherapy for early breast cancer: the Anglo Celtic Group OPTION trial”. Annals of Oncology 28.8 (2017): 1811-1816. 
  32. Demeestere I., et al. “No Evidence for the Benefit of Gonadotropin-Releasing Hormone Agonist in Preserving Ovarian Function and Fertility in Lymphoma Survivors Treated with Chemotherapy: Final Long-Term Report of a Prospective Randomized Trial”. Journal of Clinical Oncology 34.22 (2016): 2568-2574. 
  33. Del Mastro L and Lambertini M. “Temporary Ovarian Suppression with Gonadotropin-Releasing Hormone Agonist During Chemotherapy for Fertility Preservation: Toward the End of the Debate?”. Oncologist 20.11 (2015): 1233-1235. 
  34. Roness H., et al. “Prevention of chemotherapy-induced ovarian damage: possible roles for hormonal and non-hormonal attenuating agents”. Human Reproduction Update 20.5 (2014): 759-774. 
  35. Henry L., et al. “Supplementation of transport and freezing media with anti-apoptotic drugs improves ovarian cortex survival”. Journal of Ovarian Research 9.4 (2016). 
  36. Li S., et al. “Sphingosine-1-phosphate activates the AKT pathway to inhibit chemotherapy induced human granulosa cell apoptosis”. Gynecological Endocrinology 33.6 (2017): 476-479. 
  37. Li F., et al. “Sphingosine-1-phosphate prevents chemotherapy-induced human primordial follicle death”. Human Reproduction 29.1 (2014): 107-113. 
  38. Morgan S., et al. “Cisplatin and doxorubicin induce distinct mechanisms of ovarian follicle loss imatinib provides selective protection only against cisplatin”. PloS one 8.7 (2013): e70117. 
  39. Kerr J., et al. “DNA damage-induced primordial follicle oocyte apoptosis and loss of fertility require TAp63-mediated induction of Puma and Noxa”. Molecular Cell 48.3 (2012): 343-352. 
  40. Kato K. “Vitrification of embryos and oocytes for fertility preservation in cancer patients”. Reproductive Medicine and Biology 15.4 (2016): 227-233. 
  41. Kano M., et al. “AMH/MIS as a contraceptive that protects the ovarian reserve during chemotherapy”. Proceedings of the National Academy of Sciences of the United States of America 114.9 (2017): E1688-E1697. 
  42. Jang H., et al. “Melatonin prevents cisplatin‐induced primordial follicle loss via suppression of PTEN/AKT/FOXO3a pathway activation in the mouse ovary”. Journal of Pineal Research 60.3 (2016): 336-347. 
  43. Kalich-Philosoph L., et al. “Cyclophosphamide triggers follicle activation and "burnout" AS101 prevents follicle loss and preserves fertility”. Science Translational Medicine 5.185 (2013): 185ra62. 
  44. Roness H., et al. “Ovarian follicle burnout: A universal phenomenon?”. Cell Cycle 12.20 (2013): 3245-3246. 
  45. Ben-Aharon I., et al. “Chemotherapy-Induced Ovarian Failure as a Prototype for Acute Vascular Toxicity”. Oncologist 17.11 (2012): 1386-1393. 
  46. Skaznik-Wikiel ME., et al. “Granulocyte colony-stimulating factor with or without stem cell factor extends time to premature ovarian insufficiency in female mice treated with alkylating chemotherapy”. Fertility and Sterility 99.7 (2013): 2045-2054. 
  47. Bostancı MS., et al. “The protective effect of G-CSF on experimental ischemia/reperfusion injury in rat ovary”. Archives of Gynecology and Obstetrics 293.4 (2016): 789-795.
  48. Akdemir A., et al. “Granulocyte-colony stimulating factor decreases the extent of ovarian damage caused by cisplatin in an experimental rat model”. Gynecologic Oncology 25.4 (2014): 328-333. 
  49. Liang Y., et al. “Protective effects of melatonin agonist on radiotherapy-induced ovarian damage in rats”. International Journal of Clinical and Experimental Medicine 9.2 (2016): 4023-4028.
  50. Jang H., et al. “Melatonin and Fertoprotective Adjuvants: Prevention against Premature Ovarian Failute during Chemotherapy”. International Journal of Molecular Sciences 18.6 (2017): 1221. 
  51. Sonigo C., et al. “The past, present and future of fertility preservation in cancer patients”. Future Oncology 11.19 (2015): 2667-2680. 
  52. Amorim CA and Shikanov A. “The artificial ovary: current status and future perspectives”. Future Oncology 12.19 (2016): 2323-2332. 
  53. Johannesson L and Järvholm S. “Uterus transplantation: current progress and future prospects”. International Journal of Women's Health 8 (2016): 43. 
  54. Brännström M., et al. “Livebirth after uterus transplantation”. Lancet 38.9968 (2015): 607-616.
  55. Brannstrom M., et al. “Global results of human uterus transplantation and strategies for pre-transplantation screening of donors”. Fertility and Sterility 112.1 (2019): 3-10. 
  56. Telfer EE and Fauser BC. “Important steps towards materializing the dream of developing an artificial ovary”. Reproduction Biomed Online 33.3 (2016): 333-334.
Citation: Amanda Farrugia and Jean Calleja Agius . “Future Fertility of Women Cancer Survivors: The Progress in Fertility Preservation”. EC Gynaecology 9.3 (2020): 01-08.

PubMed Indexed Article

EC Pharmacology and Toxicology
LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.

PMID: 31143884 [PubMed]

PMCID: PMC6536005

EC Pharmacology and Toxicology
Alzheimer's Pathogenesis, Metal-Mediated Redox Stress, and Potential Nanotheranostics.

PMID: 31565701 [PubMed]

PMCID: PMC6764777

EC Neurology
Differences in Rate of Cognitive Decline and Caregiver Burden between Alzheimer's Disease and Vascular Dementia: a Retrospective Study.

PMID: 27747317 [PubMed]

PMCID: PMC5065347

EC Pharmacology and Toxicology
Will Blockchain Technology Transform Healthcare and Biomedical Sciences?

PMID: 31460519 [PubMed]

PMCID: PMC6711478

EC Pharmacology and Toxicology
Is it a Prime Time for AI-powered Virtual Drug Screening?

PMID: 30215059 [PubMed]

PMCID: PMC6133253

EC Psychology and Psychiatry
Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse.

PMID: 30417173 [PubMed]

PMCID: PMC6226033

EC Anaesthesia
Arrest Under Anesthesia - What was the Culprit? A Case Report.

PMID: 30264037 [PubMed]

PMCID: PMC6155992

EC Orthopaedics
Distraction Implantation. A New Technique in Total Joint Arthroplasty and Direct Skeletal Attachment.

PMID: 30198026 [PubMed]

PMCID: PMC6124505

EC Pulmonology and Respiratory Medicine
Prevalence and factors associated with self-reported chronic obstructive pulmonary disease among adults aged 40-79: the National Health and Nutrition Examination Survey (NHANES) 2007-2012.

PMID: 30294723 [PubMed]

PMCID: PMC6169793

EC Dental Science
Important Dental Fiber-Reinforced Composite Molding Compound Breakthroughs

PMID: 29285526 [PubMed]

PMCID: PMC5743211

EC Microbiology
Prevalence of Intestinal Parasites Among HIV Infected and HIV Uninfected Patients Treated at the 1o De Maio Health Centre in Maputo, Mozambique

PMID: 29911204 [PubMed]

PMCID: PMC5999047

EC Microbiology
Macrophages and the Viral Dissemination Super Highway

PMID: 26949751 [PubMed]

PMCID: PMC4774560

EC Microbiology
The Microbiome, Antibiotics, and Health of the Pediatric Population.

PMID: 27390782 [PubMed]

PMCID: PMC4933318

EC Microbiology
Reactive Oxygen Species in HIV Infection

PMID: 28580453 [PubMed]

PMCID: PMC5450819

EC Microbiology
A Review of the CD4 T Cell Contribution to Lung Infection, Inflammation and Repair with a Focus on Wheeze and Asthma in the Pediatric Population

PMID: 26280024 [PubMed]

PMCID: PMC4533840

EC Neurology
Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

PMID: 28066845 [PubMed]

PMCID: PMC5214344

EC Pharmacology and Toxicology
Paradigm Shift is the Normal State of Pharmacology

PMID: 28936490 [PubMed]

PMCID: PMC5604476

EC Neurology
Examining those Meeting IOM Criteria Versus IOM Plus Fibromyalgia

PMID: 28713879 [PubMed]

PMCID: PMC5510658

EC Neurology
Unilateral Frontosphenoid Craniosynostosis: Case Report and a Review of the Literature

PMID: 28133641 [PubMed]

PMCID: PMC5267489

EC Ophthalmology
OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling

PMID: 29333536 [PubMed]

PMCID: PMC5766278

EC Neurology
Longer Duration of Downslope Treadmill Walking Induces Depression of H-Reflexes Measured during Standing and Walking.

PMID: 31032493 [PubMed]

PMCID: PMC6483108

EC Microbiology
Onchocerciasis in Mozambique: An Unknown Condition for Health Professionals.

PMID: 30957099 [PubMed]

PMCID: PMC6448571

EC Nutrition
Food Insecurity among Households with and without Podoconiosis in East and West Gojjam, Ethiopia.

PMID: 30101228 [PubMed]

PMCID: PMC6086333

EC Ophthalmology
REVIEW. +2 to +3 D. Reading Glasses to Prevent Myopia.

PMID: 31080964 [PubMed]

PMCID: PMC6508883

EC Gynaecology
Biomechanical Mapping of the Female Pelvic Floor: Uterine Prolapse Versus Normal Conditions.

PMID: 31093608 [PubMed]

PMCID: PMC6513001

EC Dental Science
Fiber-Reinforced Composites: A Breakthrough in Practical Clinical Applications with Advanced Wear Resistance for Dental Materials.

PMID: 31552397 [PubMed]

PMCID: PMC6758937

EC Microbiology
Neurocysticercosis in Child Bearing Women: An Overlooked Condition in Mozambique and a Potentially Missed Diagnosis in Women Presenting with Eclampsia.

PMID: 31681909 [PubMed]

PMCID: PMC6824723

EC Microbiology
Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique.

PMID: 31681910 [PubMed]

PMCID: PMC6824726

EC Neurology
Endoplasmic Reticulum-Mitochondrial Cross-Talk in Neurodegenerative and Eye Diseases.

PMID: 31528859 [PubMed]

PMCID: PMC6746603

EC Psychology and Psychiatry
Can Chronic Consumption of Caffeine by Increasing D2/D3 Receptors Offer Benefit to Carriers of the DRD2 A1 Allele in Cocaine Abuse?

PMID: 31276119 [PubMed]

PMCID: PMC6604646

EC Anaesthesia
Real Time Locating Systems and sustainability of Perioperative Efficiency of Anesthesiologists.

PMID: 31406965 [PubMed]

PMCID: PMC6690616

EC Pharmacology and Toxicology
A Pilot STEM Curriculum Designed to Teach High School Students Concepts in Biochemical Engineering and Pharmacology.

PMID: 31517314 [PubMed]

PMCID: PMC6741290

EC Pharmacology and Toxicology
Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese.

PMID: 31633124 [PubMed]

PMCID: PMC6800226

EC Neurology
Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

PMID: 29662969 [PubMed]

PMCID: PMC5898812

EC Pharmacology and Toxicology
Hyperbaric Oxygen Therapy for Alzheimer's Disease.

PMID: 30215058 [PubMed]

PMCID: PMC6133268

News and Events

January Issue Release

We always feel pleasure to share our updates with you all. Here, notifying you that we have successfully released the January issue of respective journals and the latest articles can be viewed on the current issue pages.

Submission Deadline for Upcoming Issue

ECronicon delightfully welcomes all the authors around the globe for effective collaboration with an article submission for the upcoming issue of respective journals. Submissions are accepted on/before January 17, 2022.

Certificate of Publication

ECronicon honors with a "Publication Certificate" to the corresponding author by including the names of co-authors as a token of appreciation for publishing the work with our respective journals.

Best Article of the Issue

Editors of respective journals will always be very much interested in electing one Best Article after each issue release. The authors of the selected article will be honored with a "Best Article of the Issue" certificate.

Certifying for Review

ECronicon certifies the Editors for their first review done towards the assigned article of the respective journals.

Latest Articles

The latest articles will be updated immediately on the articles in press page of the respective journals.

Immediate Assistance

The prime motto of this team is to clarify all the queries without any delay or hesitation to avoid the inconvenience. For immediate assistance on your queries please don't hesitate to drop an email to