Çocukluk Çağı Kanseri Fertilite Sonuçları

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1 Çocukluk Çağı Kanseri Fertilite Sonuçları
Doç. Dr. Batuhan Özmen Ankara Üniversitesi Tıp Fakültesi

2 Emosyonel Prediktörler
Dış Görünüm, Sağlıklı hissedebilmek Çalışabilme ve Sosyal hayat, Seksüel Fonksiyon, Ebeveyn olabilmek.

3 Endişeler !!!! Maternal riskler: Yenidoğandaki riskler
Kanser rekürrensi, İnfertilite, Gebelik Komplikasyonları ve kaybı Yenidoğandaki riskler Konjenital anomaliler, Büyüme ve gelişmenin etkilenmesi. Malignite, that their history of cancer or its treatment will have an adverse impact on their offspring conceived after cancer treatment by placing them at risk for malignancy, congenital anomalies, or impaired growth and development. They are also concerned about the risks of cancer recurrence, infertility, miscarriage, and achieving a successful pregnancy outcome.

4 Fertilite Bilgilendirmesi
>%20’si Yenidoğan potansiyel riskleri hakkında bilgi sahibidir. Despite these concerns, surveys have reported that fewer than 60 percent of respondents had received information about fertility after cancer treatment, and even fewer had received information about potential risks to offspring [1,2]. Others have reported that the rate of elective pregnancy termination among female cancer survivors was higher compared to sibling controls because of the fear that their prior cancer therapy would affect their children [3]. Patient education regarding future reproductive function is thus an important component of the care of individuals with cancer Elektif Gebelik Terminasyonu Ethics Committee of the American Society for Reproductive Medicine. Fertility preservation and reproduction in cancer patients. Fertil Steril 2005

5 Tüm Çocukluk Çağı Kanserleri Surviv oranı %70–75 (5-yıl)
Kısa Dönemde Rekürrens Sekonder Malignite Kemo-radyoterapi sekelleri (Pulmoner veya Kardiak) Uzun Dönemde POF

6

7 Gonadal Fonksiyon ve Tedaviler
Sistemik KT Kranial RT Abdominal RT Kemik İliği Transplantasyonu

8 Kemoterapi: POF ? Hipogonadizm Etki Yok
Most anticancer drugs affect dividing cells, and therefore would be expected to affect the granulosa and theca cells of the ovary more than the nondividing oocytes. However, the effect of these drugs on ovarian function varies widely, some having no effect and others causing permanent hypogonadism (table 1). Typically, the ovaries of women who received chemotherapy have normal to mildly decreased numbers of primordial follicles and a greater decrease in the numbers of larger maturing follicles [2,3], indicating a greater effect on follicular development than on oocytes. Consistent with these histology findings are the clinical observations that many women, [4-6]. Primordial fol. hafif derecede azalma Matür fol. daha ciddi azalma 8

9 Kemoterapi: POF Granüloza ve teka hücrelerine olan etki oosit azalmasından daha fazla Alkile edici ajanlar (OR= 4.0), Platin içeren ajanlar (OR = 1.8), Bitkisel alkaloidler (OR = 1.2) Anti-metabolitler (OR < 1). Cyclophosphamide is a cell cycle nonspecific drug, and as such is more cytotoxic to the ovaries than cell cycle-specific drugs, as it may harm both resting and dividing cells. 9

10 Alkylating drugs such as cyclophosphamide are the best documented and most potent at inducing ovarian failure. They alter base pairs, leading to DNA cross-links, and introduce single-strand DNA breaks [7]. As a result, they can theoretically affect both resting cells, such as oocytes, and dividing cells. The effects are age-, dose-, and drug-dependent. Younger women are affected less often than older women, presumably because they have more remaining oocytes. In one study, as an example, all women over age 40 years had amenorrhea after receiving more than 5.2 gm of cyclophosphamide, whereas the dose required to cause amenorrhea in younger women was 9.5 gm 10

11 Radyoterapi Proliferasyon kesintiye uğrar Hücre hasarı artar,
Oositler RT daha ciddi duyarlı (Mitotik inaktif ?)  Radiation therapy is more damaging to ovarian tissue than is chemotherapy. Its effects also are dose- and age-dependent, but unlike chemotherapy radiation it is particularly toxic to oocytes [14]. Radiation toxicity varies with the cell cycle, being greatest during mitosis prenatally, the early stages of the first meiosis, and preovulatory maturation, so that small primordial oocytes are more sensitive to radiation than are oocytes in larger follicles [14]. Especially in younger women, radiation can cause transient amenorrhea that resolves after 6 to 18 months, presumably after recruitment and development of a new cohort of primary follicles. Such a response also has been documented in women receiving radioactive iodine therapy for thyroid cancer, in whom approximately 30 percent had reversible primary hypogonadism [15]. Although doses of more than 600 rads (6 Gy) consistently cause permanent primary hypogonadism in women over age 40 years [16], the impact of lower doses varies, with reports of conceptions in women under 20 years of age who received up to 3000 rads (30 Gy) [17-19]. Treatment of women with Hodgkin's lymphoma with pelvic irradiation in addition to chemotherapy increased the risk of ovarian failure from 0 percent to 68 percent in one study [10]. 11

12 Wallace WH Int J Radiat Oncol Biol Phys 2005
RT’de Doz Etkisi Oosit için radyosensitivite <2 Gy POF (CI %98) Doğumda 20.3 Gy 10 yaşında 18.4 Gy 20 yaşında 16.5 Gy 30 yaşında 14.3 Gy > 40 yaş 6 Gy Although doses of more than 600 rads (6 Gy) consistently cause permanent primary hypogonadism in women over age 40 years [16], the impact of lower doses varies, with reports of conceptions in women under 20 years of age who received up to 3000 rads (30 Gy) [17-19]. Treatment of women with Hodgkin's lymphoma with pelvic irradiation in addition to chemotherapy increased the risk of ovarian failure from 0 percent to 68 percent in one study [10]. Wallace WH, Hum Reprod 2003 Wallace WH Int J Radiat Oncol Biol Phys 2005 12

13 Kemo-Radyoterapi A- Alkile adici ajanlar. B- RT Tek başına C- Alkile edici ajanlar ve RT birlikte (The Childhood Cancer Survivor Study. J Clin Oncol 27(14), 2009: ) 4

14 Chow et al, Pediatr Blood Cancer 2008
Kranial RT HPA aksı etkilenir (ALL) Puberte Prekoks (Düşük Doz) Santral hipogonadizm (yüksek dozlarda), G dozları aşılınca (SST ve nazofaringeal karsinomlar) CNS mechanism intrinsically responsible for restraining puberty may be more vulnerable to the effects of radiation than gonadotropin secretion by the hypothalamic–pituitary axis Chow et al, Pediatr Blood Cancer 2008

15 Chow et al, Pediatr Blood Cancer 2008
Abdominal RT POF Uterin etkiler Obstetrik komplikasyonlar (2. trimester kayıplar) CNS mechanism intrinsically responsible for restraining puberty may be more vulnerable to the effects of radiation than gonadotropin secretion by the hypothalamic–pituitary axis Chow et al, Pediatr Blood Cancer 2008

16 RT’nin Uterus Üzerine etkisi
Muskuler tabakada kısıtlanmış büyüme Kan akımında azalma, Endometrial hasar Yüksek oranda obstetrik komplikasyon (<1 yıl) Uterin vasküler yapı sitotrofoblastik invazyona normal yanıt veremez; Düşük dirençli büyük damarlara dönüşüm olmaz. Fibrin depolanması, nekroz ve skleroz gibi direkt hasar Azalmış fetoplasental kan akımı Azalmış uterin elastikiyet ve hacim Endometrial hasar ve abdominal desudializasyon, POF dozundan daha düşük ( cGy)

17 Abdominal ve Kranial RT
Çalışma Hasta sayısı Tanı Tedavi Tedavi sonrası gonadal fonksiyonlar ALL, Akut lenfoblastik lösemi; POF, premature ovarian yetmezlik Shalet et al.33 18 Abdominal tm 20–30 Gy abdominal %100 POF Hamre et al.35 97 ALL 18–24 Gy cranially 18–24 Gy craniospinally   12 Gy abdominally %9 POF %49 POF %93 POF Wallace et al.34 38 15 Wilm’s tümör Diğer abd tm 20–30 Gy flank %71 pubertal yet. %26 POF %6 pubertal yet. Schuck et al.36 10 8 19 Abdominal neoplazm 15–60 Gy her iki over 38–56 Gy pelvik alan 12–54 Gy tek over %90 POF %88 POF %47 POF

18 Kemo-Radyoterapi: AA Doz Düşürülmesi
Çalışma Tanı Tedavi Gonadal Etki Whitehead HD MOPP + Dia. üstü RT %0 POF Green Non-Hodgkin AA AA + abdominal RT %100 POF Byrne Tüm malign Relatif fertilite 1.02 Wallace Osteosarkom CP veya DXR %43 POF Clayton Beyin tm RT + kemoterapi %77 Puberte yet Mackie ChlVPP %38 POF van den Berg MOPP · 3, ABVD · 3 %53 POF Maneschi et al. ALL AA + Kranial RT Wikstro¨ m %10 POF MOPP · 6 ABVD · 6 MOPP/ABVD · 3

19 Kemik İliği Transplant: POF
Çalışma Tanı Tedavi Gonadal Fonksiyon Leiper et al. Akut lösemi AA + TBI %100 POF Barrett et al Belirtilmemiş TBI Sarafoglou et al Akut Lösemi Teinturier et al. Nöroblastom, sarkom, lenfoma AA Busulfan dahil AA Busulfan hariç %100’de POF %22’de POF Thibaud et al. Miks Kanserler ve anemi AA tek başına AA + TVI (12 Gy) TVI tek başına (10 Gy) TA RT (5–6 Gy) %70 POF %11 POF %71 POF Couto-Silva et al. Miksed anserler ve anemiler TVI (2 Gy · 6) TVI (10 Gy · 1) TLI (5–6 Gy · 1) AA %86 POF %88 POF %43 POF %60 POF Larsen et al Lösemi Lenfoma AA + TVI

20 KİT Sonrası Gonadal Fonksiyonlar
Alkile edici KT ve/veya Tüm vücut RT 19 412 allojenik + 17 950 otolog KIT 113 gebe (%0.6) 30 ART (10 İVF,4 Oİ, 16 sperm kriyo) pretransplant conditioning protocol have a particularly high risk of ovarian failure Salooja et al. Lancet 2001

21 Risk Faktörleri: POF İleri yaş
Over dokusuna artmış RT maruziyeti (≥1000-cGy), Artmış AA skoru (Ajan sayısı + kümülatif doz), Abdominal RT + KT Hodgkin's lenfoma tanısı The cumulative incidence of nonsurgical premature menopause was approximately 30 percent in survivors who had been treated with both alkylating agents and abdominopelvic radiation

22 AMH + Inhibin B Tedavi Sonrası Takip 2-5 gün Düzenli sikluslar ?.
Küçük over hacmi Yüksek E2 2-5 gün AMH + Inhibin B

23 Garcia CR Fertil Steril. 2012

24 AMH ve POF İlişkisi: All CCS (n = 182) AMH < 0.1 µg/l (n = 17)
Age at treatment (years) 5.8 (0.1–16.8) 10.4 (1.1–16.1) 5.3 (0.14–16.8) <0.05 Menstrual cycle (n; %) Regular  33 2 (6%) 31 (94%) <0.001 Oligo- or amenorrhea  28 4 (14%) 24 (86%) Oral contraceptive pills  98 5 (5%) 93 (95%) Time of treatment (n; %) Prior to menarche  114 5 (4%) 109 (96%) <0.01 After menarche  31 7 (23%) 24 (77%) Diagnosis (n; %) Leukaemia group (ALL and NHL)  77 4 (5%) 73 (95%) AML  8 4 (50%) M Hodgkin  15 3 (20%) 12 (80%) Sarcoma  25 3 (12%) 22 (88%) Wilms tumour  3 (11%) 25 (89%) Treatment (n; %) Chemotherapy and radiotherapy  63 15 (24%) 48 (76%) Radiotherapy on abdomen or total body  14 9 (64%) 5 (36%) Lie Fong S et al. Hum. Reprod. 2009;24:

25 AMH Düzeyi: Güvenle kullanılabilinir (<0.5- 1 ng/mL)
%53 AMH düşük (FSH normal) En düşük AMH KIT Hodgkin Lf Sarkomlarda Prokarbazin (CED yüksekliği) OKS kullanımı Chapentier J cancer surviv 2014

26 Korunma Stratejileri GnRH-a uygulanması Oosit kriyopreservasyonu, Embriyo kriyopreservasyonu. Over dokusu kriyopreservasyonu Overin transpozisyonu

27 Çocukluk Çağı Kanserleri ve Gebelik
Gebelik OR 0.81, %95, CI Eger RT almamış veya 0.01 Gy alan, OR 1.07, %95, CI Infertilite Riski OR 1.18, %95, CI Prematur Menapoz OR 13.21, %95, CI

28 Çocukluk Çağı Kanserleri ve Gebelik
Doğal Gebelik Sonuçları Canlı Doğum (n = 2,998) Düşük (n = 607) n (%) OR (95% CI) Lösemi (referans) 549 (69.4%) 1 132 (16.7%) Hodgkin lenfoma 251 (72.5%) 1.2 ( ) 49 (14.2%) 0.8 ( ) NHL 156 (74.6%) 1.4 ( ) 28 (13.4%) 0.7 ( ) SSS Tümörler 577 (77.0%) 1.5 ( ) 90 (12.0%) 0.7 ( ) Nöroblastoma 139 (73.5%) 1.4 ( ) 29 (15.3%) 0.8 ( ) NH-retinoblastoma 213 (77.7%) 1.5 ( ) 33 (12.0%) 0.7 ( ) H-retinoblastoma 83 (73.5%) 1.5 ( ) 13 (11.5%) 0.6 ( ) Wilms Tümörü 248 (65.6%) 1.0 ( ) 66 (17.5%) 1.0 ( ) Kemik Tümörleri 180 (71.9%) 37 (14.9%) 0.9 ( ) Yumuşak Doku Sarkom 241 (71.9%) 58 (17.3%) 1.0 ( ) Dİğer 361 (75.0%) 1.2 ( ) 72 (15.0%) 0.8 ( ) P heterogeneity 0.492 0.45 Raoul C. et al Cancer Epidemiol Biomarkers Prev 2009

29 Kötü Prognoz Belirteçleri
Hypothalamic/pituitary RT dozu ≥30 Gy, Over/Uterus RT dozu >5 Gy, KIT AA skoru > 3-4 Lomustine veya cyclophosphamide  The relative risk for female survivors of ever being pregnant was 0.81 (95% CI, ) compared with female siblings; poor prognostic factors included hypothalamic/pituitary radiation dose ≥30 Gy, an ovarian/uterine radiation dose >5 Gy, a summed alkylating agent dose score of three or four, or treatment with lomustine or cyclophosphamide  29

30 Abdominal RT Gebelik Sonuçları
Reproductive Outcomes for Survivors of Childhood Cancer. Hudson, Melissa Obstetrics & Gynecology. 116(5): , November 2010. DOI: /AOG.0b013e3181f87c4b Table 2. Relationship Between Flank Radiation and Pregnancy Outcomes in Female Survivors of Wilms Tumor 5

31 Konjenital Anomali Riski; Kemoterapi
Doğumsal defektlerde artmış risk yoktur, Konjenital malformasyonlar %2.6 (kanser survivor) vs 2.3% (kardeşleri) IR 1.2 vs non-IR 1.0 (95% CI, 0.7–2.0) 1056 children born to male and female survivors treated with therapies that are potentially mutagenic to germ cells, no increase in birth defects was observed A recent population-based cohort study of 1715 offspring of 3963 childhood cancer survivors, and 6009 offspring of 5657 survivors’ siblings, found 44 (2.6%) cases of congenital malformations in the study group compared with 140 (2.3%) in the control group, which was not statistically different. slightly but insignificantly higher risk of malformations in the offspring of irradiated parents compared with nonirradiated parents. Artmış risk bulunmamıştır Hawkins MM, J Natl Cancer Inst 1991 Winther et al, Clin Genet 2009 Barton MK CA Cancer Clin 2012

32 Konjenital Anomali Riski; Radyoterapi
RT almamışlarda konjenital anomali riski 3/93 (3.2 %) RT alan 2/61 (3.3 %) Gy RT alan 8/76 (%10.4 ) >25 Gy RT alan kadınlar 6/60 (%10) Green DM, J Clin Oncol 2002 Whinter JF, Br J Can 2009

33 Malignite Riski: Offspring
Çalışma Hasta sayısı Malign Sonuç Mulvihill et al. 2283 CCS 2308 çocuk 3604 sağlıklı kardeşte 4719 çocuk 7 11 Artmış risk yoktur Scand. Study CCS 5847 cocuk 44 Non-Herediter CA risk artışı yok Mulvihill et al.52 analysed the risk of cancer in 2308 offspring of 2283 long-term survivors, males as well as females, of childhood cancer. He found seven cases of cancer in the study group and 11 cases in the 4719 offspring of 3604 healthy sibling controls. The observed numbers of cases were not significantly different from those expected in the general population. These findings are supported by a later and larger Scandinavian study assessing the risk of cancer among 5847 offspring of 14 652 childhood cancer survivors.53 Forty-four malignant neoplasms were diagnosed (standardised incidence ratio, 2.6; 95% CI, 1.9–3.5). Of these, 17 were retinoblastomas (compared with an expected 0.5 cases in the background population), but this is a known hereditary cancer and, indeed, 16 of these children each had a parent who had had the disease. The remaining 27 neoplasms found in the offspring were cases of nonhereditary cancers (standardised incidence ratio, 1.6; 95% CI, 1.1–2.4), and the authors conclude that there is no evidence of a significantly increased risk of nonhereditary cancer among the offspring of childhood cancer survivors. They further discourage screening for cancer in offspring of the survivors of sporadic cancer in childhood or adolescence Mulvihill, Lancet 1987 Sankila et al, N Eng J Med 1998

34 Çocukluk çağı kanser survivorlarında çocuklarında kanser riski
Inherited Predispozisyon Retinoblastoma, Li-Fraumeni sendromu ilişkili kanserler Ailesel Komponent Beyin Tümörleri Akut lösemi Pedigre analizi Prenatal Tanı PGD

35 Obstetrik Komplikasyonlar
Artmış risk….. Abortus, 2. Trimester gebelik kaybı, Preterm doğum, Düşük doğum ağırlığı, Ölü doğum – Perinatal Mortalite Anormal Plasentasyon

36 Kemoterapi: Obstetrik Komplikasyon
Eldeki veriler sıralanan riskler üzerine olumsuz etki göstermemektedir. Abortus, Fetal gelişim ve IUGR, Fetal kayıp, Uterin fonksiyonlar. The same investigators also compared pregnancy outcome in the partners of male survivors of childhood cancer to outcome in the partners of their male siblings [29]. Over 1200 male cancer survivors sired 2323 pregnancies (69 percent live births, 1 percent stillbirths, 13 percent miscarriages, 13 percent abortions, 5 percent unknown or in gestation). Although the percent of live births was higher than among female survivors (69 versus 63 percent, see above), it was significantly lower than in the partners of male siblings (69 versus 76 percent). This was due, in part, to a higher rate of pregnancy termination among the partners of male survivors compared to controls. The rate of miscarriage was similar in both cases and controls (13 versus 12.1 percent), as was the rate of stillbirth and birthweight distribution. Interestingly, this study showed a male:female sex ratio of 1.00:1.03, which is lower than that in female survivors and the general population. Possible explanations for this finding are chance and lower testosterone levels from exposure to chemotherapeutic agents [33,34]. Green DM Am J Obstet Gynecol 2002 Reulen RC, Cancer Epidemiol Biomarkers Prev 2009 Chow EJ, Arch Pediatr Adolesc Med 2009

37 Gebelik Komplikasyonları: RT
Düşük, Preterm Doğum, (50cGy->500cGy) Düşük Doğum Ağırlığı, (250cGy) Fetal gelime geriliği Plasenta akreata ve Ölü doğum [3,17,19,25,35-43]. Ancak, çalışmalar maternal faktörler için uyarlanmamıştır Maternal sigara kullanımı, Alkol kullanımı, Diyabet, Hipertansiyon, Preeklampsi, Enfeksiyon. Lie Hum Reprod 2010 Signorello Lancet 2010

38 Birthweight (in grams) in offspring of childhood cancer survivors in population-based birthweight curves per gestational age (in weeks) (Kloosterman 1969). Birthweight (in grams) in offspring of childhood cancer survivors in population-based birthweight curves per gestational age (in weeks) (Kloosterman 1969). Dashed dotted line, 2.3th and 97.7th percentile; dotted line, 10th and 90th percentile; continuous line, 50th percentile; filled triangle, offspring of survivors not treated with abdominal radiotherapy (n = 34); filled circle, offspring of survivors treated with abdominal radiotherapy (n = 6). Lie Fong S et al. Hum. Reprod. 2010;25: © The Author Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please

39 Gebelik Sonuçları: CCS
Controls (n = 9031) Whole cohort CCS (n = 40) CCS with RT to abdomen (n = 6)   Highest diastolic tension (mmHg) 81.4 (11.7) 81.9 (12.9) 80.8 (14.6) Delivery Vaginal: spontaneous  4928 (55%) 21 (52.5%) 5 (83%) Vaginal: assisted delivery  2746 (31%) 12 (30%) 1 (17%) Gestational age (weeks)  39.2 (3.0) 38.9 (2.8) 34.9 (4.3)a Birthweight (grams)  3271 (714) 3266 (705) 2503 (1, 026)* Post-partum hemorrhage No  8232 (95%) 35 (92%) 4 (67%) Yes  449 (5%) 3 (8%) 2 (33%)b Manual removal of the placenta 8430 (97%) 37 (97%) 251 (3%) 1 (3%) 1 (17%)c Lie Fong S et al. Hum. Reprod. 2010;25:

40 Not treated with radiation
Ölü Doğum Riski ve RT Not treated with radiation 1075 21 (2%) Reference Radiation dose to uterus and ovaries (Gy)    0·01–0·99 1404 24 (2%) 0·8 (0·4–1·4) 0·7‡ (0·4–1·4) 0·7§ (0·3–1·5)    1·00–2·49 155 5 (3%) 2·1 (0·8–5·7) 1·9‡ (0·7–5·4) 2·4§ (0·8–7·3)    2·50–9·99 126 5 (4%) 1·6 (0·4–6·0) 1·6‡ (0·4–6·5) 1·9§ (0·5–7·6)    ≥10·00 28 5 (18%) 9·2 (3·3–25·4) 9·1‡ (3·4–24·6) 7·3§ (2·3–23·0) Signorello Lancet. Aug 21, 2010

41 Risk of stillbirth or neonatal death
Ölü Doğum Riski ve RT Before Menarshe After Menarshe Risk of stillbirth or neonatal death Relative risk*† (95% CI) Relative risk*‡ (95% CI) No radiation 5/494 (1%) Reference 13/447 (3%) 0·01–0·99 Gy 11/636 (2%)   1·3 (0·5–3·9) 7/599 (1%) 0·3 (0·1–1·0) 1·00–2·49 Gy 3/69 (4%)   4·7 (1·2–19·0) 2/70 (3%) 1·2 (0·2–6·4) ≥2·50 Gy 11/82 (13%) 12·3 (4·2–36·0) 1/85 (1%) 0·2 (0·0–1·4) Signorello Lancet. Aug 21, 2010

42 Gebelik Monitorizasyonu
“We always carefully monitoring pregnancies however there is a limit to what we can do to prevent still births and early deaths in such patients” BBC – Health 2011

43 Öneriler Gebelik terminasyonundan kaçın!!!
Tekrarlayan gebelik kayıpları – RT Herediter kanserlerde genetik danışmanlık (PGD, AS,CVS) Plasental tutunmayı değerlendir (2-3. trimester – Doppler USG, MRI) Pregnant women who have received radiation therapy to the pelvis or abdomen are at higher risk for impaired fetal growth, placental attachment disorders, and possibly preterm labor and delivery. Placental attachment can be evaluated with sonography in the late second trimester and third trimesters. Ancillary techniques that may be used if the diagnosis is uncertain include color Doppler ultrasound examination and magnetic resonance imaging. (See "Diagnosis and management of placenta accreta".) Serial sonograms every four to six weeks in the late second and third trimesters are useful for assessing fetal growth. (See "Diagnosis of fetal growth restriction".) Weekly nonstress tests may be useful for women with a history of abdominal radiation before menarche, as they may have an increased risk for stillbirth or neonatal death. There are no reliable modalities for prediction and prevention of preterm labor and delivery

44 Öneriler IUGR (4-6 hafta ara ile USG, 2-3. trimester)
>32. hafta, haftalık NST ve MBP Doğum zamanlaması ile ilgili öneri yoktur. (Artmış ölü doğum) Pregnant women who have received radiation therapy to the pelvis or abdomen are at higher risk for impaired fetal growth, placental attachment disorders, and possibly preterm labor and delivery. Placental attachment can be evaluated with sonography in the late second trimester and third trimesters. Ancillary techniques that may be used if the diagnosis is uncertain include color Doppler ultrasound examination and magnetic resonance imaging. (See "Diagnosis and management of placenta accreta".) Serial sonograms every four to six weeks in the late second and third trimesters are useful for assessing fetal growth. (See "Diagnosis of fetal growth restriction".) Weekly nonstress tests may be useful for women with a history of abdominal radiation before menarche, as they may have an increased risk for stillbirth or neonatal death. There are no reliable modalities for prediction and prevention of preterm labor and delivery

45 Gebelik ve Rekürrens Riski
Gestasyonel trofoblastik hastalıklar dışı, Gebelik nedeni ile tanı gecikmiş olsa dahi, herhangi bir kanserin rekürrensi artmaz. Velentgas et al. Cancer 1999

46 Yastayız