title: Ovarian reserve after treatment with alkylating agents during childhood.
abstract: OBJECTIVE
  What is the effect of different alkylating agents used without pelvic radiation to treat childhood cancer in girls on the ovarian reserve in survivors?
  
  
  CONCLUSIONS
  Ovarian reserve seems to be particularly reduced in survivors who received procarbazine (in most cases for Hodgkin lymphoma) or high-dose chemotherapy; procarbazine but not cyclophosphamide dose is associated with diminished ovarian reserve.
  
  
  BACKGROUND
  A few studies have demonstrated diminished ovarian reserve in survivors after various combination therapies, but the individual role of each treatment is difficult to assess.
  
  
  METHODS
  Prospective cross-sectional study, involving 105 survivors and 20 controls.
  
  
  METHODS
  One hundred and five survivors aged 17-40 years and 20 controls investigated on Days 2-5 of a menstrual cycle or Day 7 of an oral contraceptive pill-free interval.
  
  
  METHODS
  ovarian surface area (OS), total number of antral follicles (AFC), serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol and anti-Müllerian hormone (AMH).
  
  
  RESULTS
  Survivors had a lower OS than controls: 3.5 versus 4.4 cm(2) per ovary (P = 0.0004), and lower AMH levels: 10.7 versus 22 pmol/l (P = 0.003). Ovarian markers (OS, AMH, AFC) were worse in patients who received high-dose compared with conventional-dose alkylating agents (P = 0.01 for OS, P = 0.002 for AMH, P < 0.0001 for AFC). Hodgkin lymphoma survivors seemed to have a greater reduction in ovarian reserve than survivors of leukaemia (P = 0.04 for AMH, P = 0.01 for AFC), sarcoma (P = 0.04 for AMH, P = 0.04 for AFC) and other lymphomas (P = 0.04 for AFC). A multiple linear regression analysis showed that procarbazine but not cyclophosphamide nor ifosfamide dose was associated with reduced OS (P = 0.0003), AFC (P = 0.0007), AMH (P < 0.0001) and higher FSH levels (P < 0.0001).
  
  
  CONCLUSIONS
  The small percentage of participating survivors (28%) from the total cohort does not allow conclusion on fertility issues because of possible response bias. The association between procarbazine and HL makes it impossible to dissociate their individual impacts on ovarian reserve. The number of controls is small, but ovarian volume and AMH levels in survivors were compared with published normal values and results were unchanged.
  
  
  CONCLUSIONS
  Early detection and follow-up of compromised ovarian function after cancer therapy should help physicians to counsel young survivors about their fertility window. However, longitudinal follow-up is required to determine the rate of progression from low ovarian reserve to premature ovarian failure.
  
  
  BACKGROUND
  La Ligue contre le Cancer (grant no., PRAYN7497). The authors have no competing interests to disclose.
authors: Department of Paediatric Endocrinology, APHP, Hopital de Bicêtre, rue du Général Leclerc, Le Kremlin Bicêtre F-94270, France Radiation Epidemiology Group, Centre for Research in Epidemiology and Population Health (CESP)-INSERM U1018, Institut Gustave Roussy, rue Edouard Vaillant Villejuif F-94805, France cecile.teinturier@bct.aphp.fr.
authors: Cécile
authors: C
authors: Thomas-Teinturier
authors: Radiation Epidemiology Group, Centre for Research in Epidemiology and Population Health (CESP)-INSERM U1018, Institut Gustave Roussy, rue Edouard Vaillant Villejuif F-94805, France.
authors: Rodrigue Sétchéou
authors: RS
authors: Allodji
authors: Department of Paediatric Oncology, Institut Gustave Roussy, rue Edouard Vaillant Villejuif F-94805, France.
authors: Ekaterina
authors: E
authors: Svetlova
authors: Department of Paediatric Oncology, Institut Gustave Roussy, rue Edouard Vaillant Villejuif F-94805, France.
authors: Marie-Alix
authors: MA
authors: Frey
authors: Department of Paediatric Oncology, Institut Gustave Roussy, rue Edouard Vaillant Villejuif F-94805, France.
authors: Odile
authors: O
authors: Oberlin
authors: Department of Paediatric Radiology, APHP, Hopital Necker, rue de Sevres Paris F-75015, France.
authors: Anne-Elodie
authors: AE
authors: Millischer
authors: Department of Gynaecology, APHP, Hopital Bichat, rue Henri Huchart, Paris F-75018, France.
authors: Sylvie
authors: S
authors: Epelboin
authors: Fertility Preservation Unit, Lille University, Hopital Jeanne de Flandre, avenue Eugene Avinee Lille F-59000, France.
authors: Christine
authors: C
authors: Decanter
authors: Department of Paediatric Oncology, Institut Curie, rue d'Ulm, Paris F-75005, France.
authors: Helene
authors: H
authors: Pacquement
authors: Department of Paediatric Oncology, APHP, Hopital Trousseau, avenue du Dr Arnold Netter, Paris F-75012, France.
authors: Marie-Dominique
authors: MD
authors: Tabone
authors: Department of Paediatric Oncology, Centre Oscar Lambret, rue Frederic Combemale Lille F-59000, France.
authors: Helene
authors: H
authors: Sudour-Bonnange
authors: Department of Paediatric Hematology, APHP, Hopital Robert Debre, boulevard Serurier, Paris F-75019, France.
authors: André
authors: A
authors: Baruchel
authors: Laboratory of Hormonal Biology, APHP, Hopital Cochin, rue du faubourg Saint-Jacques, Paris F-75005, France.
authors: Najiba
authors: N
authors: Lahlou
authors: Radiation Epidemiology Group, Centre for Research in Epidemiology and Population Health (CESP)-INSERM U1018, Institut Gustave Roussy, rue Edouard Vaillant Villejuif F-94805, France University Paris-Sud XI, Villejuif F-94800, France.
authors: Florent
authors: F
authors: De Vathaire
mesh_terms: D000293:Adolescent; D000328:Adult; D054304:Anti-Mullerian Hormone / Q000097:blood; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects* / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006689:Hodgkin Disease / Q000188:drug therapy*; D006801:Humans; D016014:Linear Models; D007986:Luteinizing Hormone / Q000097:blood; D065851:Ovarian Reserve / Q000187:drug effects*; D010053:Ovary / Q000000981:diagnostic imaging / Q000187:drug effects; D011344:Procarbazine / Q000009:adverse effects* / Q000627:therapeutic use; D011446:Prospective Studies; D017741:Survivors; D014463:Ultrasonography
chemical_list: D018906:Antineoplastic Agents, Alkylating; D011344:Procarbazine; D004958:Estradiol; D054304:Anti-Mullerian Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone
keywords: AMH; chemotherapy; childhood cancer survivors; hodgkin lymphoma; ovarian reserve