© Borgis - Postępy Nauk Medycznych 4/2014, s. 283-287
*Marzena Samardakiewicz1, Ewa Pałka2, Karolina Piecak2, Agnieszka Zaucha-Prażmo1
Kriokonserwacja kory jajnika u dziewcząt i młodych kobiet z rozpoznaniem nowotworu
Cryopreservation of ovarian cortex in girls and young women diagnosed with cancer
1Department of Pediatrics Hematology, Oncology and Transplantology, Medical University, Lublin
Head of Department: prof. Jerzy R. Kowalczyk, MD, PhD
2Students’ Scietific Society, Department of Pediatrics Hematology, Oncology and Transplantology, Medical University, Lublin
Head of Department: prof. Jerzy R. Kowalczyk, MD, PhD
Tutor: Marzena Samardakiewicz PhD, MA
Streszczenie
W ostatnich czasach, dzięki niezwykłemu postępowi medycyny i stosowaniu coraz agresywniejszych form leczenia przeciwnowotworowego, rośnie liczba ozdrowieńców. Obecnie w Polsce 5% osób z nowo rozpoznaną chorobą nowotworową to osoby poniżej 35 roku życia, a więc w wieku prokreacyjnym. Należy zwrócić szczególną uwagę na jakość ich życia. Z jakością życia wiąże się wiele różnych aspektów, m. in. chęć posiadania potomstwa. W przypadku dziewczynek i młodych kobiet skuteczne leczenie przeciwnowotworowe powinno być zatem poprzedzone propozycją odpowiedniej metody umożliwiającej zachowanie płodności. Jedną z takich metod jest kriokonserwacja kory jajnika.
Kriokonserwacja kory jajnika jest eksperymentalną, ale bardzo obiecującą metodą zachowania płodności, skierowaną przede wszystkim do młodych kobiet, również przed okresem pokwitania. W przeciwieństwie do innych metod, nie wymaga stymulacji hormonalnej przed pobraniem tkanki, dzięki czemu nie opóźnia leczenia przeciwnowotworowego. Po upływie przynajmniej 2 lat od zakończenia leczenia i wykluczenia nawrotu choroby można przeszczepić tkankę jajnika w sposób orto- lub heterotopowy.
Celem pracy jest uświadomienie lekarzom konieczności informowania kobiet jeszcze przed rozpoczęciem leczenia przeciwnowotworowego o metodach zachowania płodności.
Summary
In the last years, thanks to an incredible development of medicine and using more aggressive forms of cancer treatment, the number of cancer survivors increases. Currently in Poland, 5% of people diagnosed with cancer are under 35 years old, which means in procreative age. It is particularly important to pay attention to the standard of their lives. It is correlated with many aspects, also the will to have children. In cases of girls and young women, an effective cancer treatment should be preceded by an offer of a proper method enabling fertility preservation. One of such methods is cryopreservation of ovarian cortex.
Cryopreservation of ovarian cortex is an experimental, but very promising method of preserving fertility especially for young women, also before puberty. In contrast to other methods, requires no hormonal stimulation prior to collection the tissue so it doesn’t delay cancer therapy. After at least 2 years from the end of cancer treatment and exclusion of recurrent disease, ovarian tissue can be transplanted ortho- or heterotopic.
The aim of the study is to emphasize the need to inform women about the fertility preservation methods even before the cancer treatment. The issue of the fertility preservation is becoming increasingly essential due to the growing number of the cancer survivors.
Introduction
It is estimated that ca. 700 thousand to 1 million couples in Poland suffer from infertility (transient or constant), induced by male or female factor. There are many reasons of infertility, e.g. immunological disorders, semen anomalies, endometriosis, sexually transmitted diseases (STD) or cancer treatment. The cancer itself may diminish fertility by malnutrition syndrome, depression, elevated temperature, opportunistic infections. During the next decade the number of people with infertility caused by cancer treatment will probably increase (1-3).
Fertility among oncological female patients may be diminished by the decrease of the number of ovarian follicles, hormonal disorders or malfunction of reproductive system. Infertility may occur already during treatment as period loss or a few years after the completion of treatment as premature ovarian failure (POF). Even after the reoccurrence of period after the completion of treatment, fertility may be highly disordered. The transient loss of period is caused by damage to mature follicles, while lasting loss – by damage to both mature and primary follicles (4).
The risk of infertility is closely correlated with treatment method, duration of treatment, doses, application method, cancer type, as well as age of a patient and her fertility before the treatment (often difficult to estimate) (tab. 1) (5).
Table 1. The risk of amenorrhea depending on the treatment (6).
| Level of risk | Treatment protocol | Application |
High risk
Among > 80% of women suffer from amenorrhea | 1. Irradiation of abdomen or pelvis with doses > 6 Gy among adult women, > 15 Gy among women before puberty and > 10 Gy after puberty
2. TBI
3. CMF, CEF, CAF w 6 in among women > 40 y.o.
4. Cyclophosphamide 5 g/m2 among women > 40 y.o. and 7.5 g/m2 among women < 20 y.o.
5. Alkylating agents prior to BMT/SCT
6. Alkylating agents together with TBI or pelvis irradiation
7. Protocols containing procarbazine
8. Irradiation of skull/brain > 40 Gy | 1. Various cancer types
2. BMT/SCT
3. Breast cancer
4. Various cancer types
5. BMT/SCT
6. BMT/SCT, HL, neuroblastoma, ovary cancer
7. HL
8. Brain cancer |
Medium risk
30-70%
| 1. CMF, CEF, CAF w 6 in among women 30-39 y.o.
2. AC among women > 40 y.o.
3. Irradiation of abdomen or pelvis in 10-15 Gy before puberty
4. Irradiation of abdomen or pelvis in 5-10 Gy after puberty
5. Irradiation of spine with doses > 25 Gy | 1. Breast cancer
2. Breast cancer
3. Wilms’ tumor
4. Wilms’ tumor, neuroblastoma
5. Spine, brain cancer, return of ALL, NHL |
Low risk
< 20%
| 1. CMF, CEF, CAF w 6 in among women < 30 y.o.
2. AC among women 30-39 y.o.
3. Protocol ABVD, CHOP, COP
4. AC
5. Multidrug therapy | 1. Breast cancer
2. Breast cancer
3. HL, NHL
4. AML
5. ALL |
Very low/no risk
| 1. Methotrexate, 5-fluorouracil
2. Vincristine in politherapy
3. Radioactive iodine
| 1. Breast cancer
2. Leukemia, HL, NHL, neuroblastoma, Wilms’ tumor
3. Thyroid cancer |
Gy – Grey; HL – Hodgkin’s lymphoma; TBI – Total Body Irradiation; BMT – Bone Marrow Transplant; SCT – Stem Cell Transplant; NHL – Non-Hodgkin lymphoma; AML – acute marrow leukemia; ALL – acute lymphoblastic leukemia; AC, CMF, CEF, CAF, ABVD, CHOP, COP – treatment schemes
Based on the data of National Register of Cancer in years 1999 and 2009, a significant increase of cancer survivors can be seen, due to major medical progress and even more aggressive forms of treatment. Currently 5% (ca. 7000 a year) of people diagnosed with cancer are below 35 years of age. It is very important to pay attention to the standard of their lives.
Among the majority of young women diagnosed with cancer, the desire to become a mother in the future becomes stronger than before diagnosis, although some of them fear parenthood because of the possibility of disease recurrence. During the study it was stated that s much as 81% of patients and 93% of their parents was interested in the possibility of fertility preservation (7).
Taking into consideration the information above, doctors should talk to the patient and explain possible consequences of cancer treatment, as well as propose a method of fertility preservation (fig. 1) (8-11).
Fig 1. Female fertility preservation options.
IVF – in vitro fertilization; IVM – maturation of cells in vitro, GnRH – gonadoliberyna
Cryopreservation of ovarian cortex
Cryopreservation of embryos and in vitro fertilization (IVF) is a widely accepted method that requires certain age of a patient (after puberty) and ovaries stimulation (in case of hormone-dependent cancer the ovaries are stimulated with tamoxifen and aromatase inhibitors). Mainly, it is a method for patients who have a partner or are willing to use the service of semen bank. A sure advantage of IVF is a big percentage of pregnancies ended with birth (effectiveness of 40%).
Cryopreservation of ovarian cortex is still an experimental, but very promising method that is possible also for women before puberty. This method still needs a lot of research concerning its safety and effectiveness and the use of this method requires approval of bioethical board.
On the contrary to other methods of fertility preservation, it does not require hormonal stimulation prior to collection of tissue, which does not delay the treatment. However, the method is not recommended to women after 40 years of age due to low ovarian reserve. Ovarian reserve amounts to 300 thousand egg cells at the moment of birth and decrease with age. Currently, it is estimated that among 95% of women above 30 years of age the amount of egg cells is ca. 12% of primary ovarian reserve, and among women above 40 years of age – only 3%.
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Piśmiennictwo
1. Radwan J: Epidemiologia niepłodności. [W:] Radwan J, Wołczyński S (red.): Niepłodność i rozród wspomagany. Termedia, Poznań 2011: 11-14.
2. Kurzawa R, Kaniewska D, Bączkowski T: Niepłodność jako problem kliniczny i społeczny. Przew Lek 2010; 2: 149-152.
3. Mazur-Roszak M, Tomczak P, Litwiniuk M et al.: Niepłodność w onkologii – wybrane zagadnienia. Część II. Ochrona funkcji rozrodczych. Współcz Onkol 2005; 9: 65-68.
4. Meirow D, Nugent D: The effects of radiotherapy and chemotherapy on female reproduction. Hum Reprod Update 2001; 7: 535-543.
5. Pentheroudakis G, Pavlidis N, Castiglione N: Cancer, fertility and pregnancy: ESMO Clinical Recommendations for diagnosis, treatment and follow-up. Ann Oncol 2009; 20: 178-181.
6. www.fertilehope.org.
7. Schover L: Motivation for parenthood after cancer: A Review. J Natl Cancer Inst Monogr 2005; 34: 2-5.
8. Hilaly A: Preservation of ovarian function in the cancer patient. ASJOG 2006: 3.
9. Sonmezer M, Oktay K: Fertility preservation in female patients. Hum Reprod Update 2004; 10: 251-266.
10. Oktay K, Oktem O: Fertility preservation medicine: a new field in the care of young cancer survivors. Pediatr Blood Cancer 2009; 53: 267-273.
11. Wallberg K, Keros V, Hovatta O: Clinical aspects of fertility preservation in female patients. Pediatr Blood Cancer 2009; 53: 254-260.
12. Bidziński M, Zalewski K: Zachowanie zdolności prokreacyjnych w aspekcie choroby nowotworowej. [W:] Radwan J, Wołczyński S (red.): Niepłodność i rozród wspomagany. Termedia, Poznań 2011: 259-275.
13. Wolff M, Montag M, Dittrich R et al.: Fertility preservation in women – a practical guide to preservation techniques and therapeutic strategies in breast cancer, Hodgkin’s lymphoma and borderline ovarian tumours by the fertility preservation network FertiPROTEKT. Arch Gynecol Obstet 2011; 284: 427-435.
14. Radwan J, Wołczyński S: Fizjologia i endokrynologia rozrodu. [W:] Radwan J, Wołczyński S (red.): Niepłodność i rozród wspomagany. Termedia, Poznań 2011: 32-44.
15. Silber S, Lenahan K, Levine D et al.: Ovarian transplantation between monozygotic twins discordant for premature ovarian failure. N Engl J Med 2005; 353: 58-63.
16. Radwan P: Kriokonserwacja w rozrodzie wspomaganym. [W:] Radwan J, Wołczyński S (red.): Niepłodność i rozród wspomagany. Termedia, Poznań 2011: 217-224.
17. Meirow D, Levron J, Eldar-Geva T: Pregnancy after transplantation of cryopreserved ovarian tissue in a patient with ovarian failure after chemotherapy. N Engl J Med 2005; 353: 318-321.
18. Meirow D, Yehuda DB, Prus D et al.: Ovarian tissue banking in patients with Hodgkin’s disease: is it safe? Fertil Steril 1998; 69: 996-998.
19. Kim S, Radford J, Harris M et al.: Ovarian tissue harvested from lymphoma patients to preserve fertility may be safe for autotransplantation. Hum Reprod 2001; 16: 2056-2060.
20. Gosden R, Rutherford A, Norfolk D: Transmission of malignant cells in ovarian grafts. Hum Reprod 1997; 12: 403-405.
21. Kim S, Kang H, Kim N et al.: Assessment of the integrity of human oocytes retrieved from cryopreserved ovarian tissue after xenotransplantation. Hum Reprod 2005; 20: 2502-2508.
22. Demeestere I, Simon P, Emiliani S et al.: Orthotopic and heterotopic ovarian tissue transplantation. Hum Reprod Update 2009; 15: 649-665.
23. Salle B, Demirci B, Franck M et al.: Normal pregnancies and live births after autografts of frozen-thawed hemi-ovaries into ewes. Feril Steril 2002; 77: 403-408.
24. Beck L: The gift of hope: my personal experience. J Natl Cancer Inst Monogr 2005; 34: 1-2.
