TY  - CHAP
M1  - Book, Section
TI  - Genetic Basis of Female Infertility
A1  - Dukhovny, Stephanie
A1  - Wilkins-Haug, Louise
A2  - Murray, Michael F.
A2  - Babyatsky, Mark W.
A2  - Giovanni, Monica A.
A2  - Alkuraya, Fowzan S.
A2  - Stewart, Douglas R.
PY  - 2014
T2  - Clinical Genomics: Practical Applications in Adult Patient Care
AB  - Disease  summary:Infertility  is  defined  as  failure  to  conceive  in  the  setting  of  regular  intercourse  within  1  year  for  women  younger  than  35  years  within  6  months  for  women  older  than  35  years.  The  prevalence  of  infertility  is  between  7%  and  15%.  There  are  many  causes  of  infertility,  with  estimates  of  female  factor  infertility  as  an  explanation  in  up  to  37%  of  couples  and  both  male  and  female  factor  infertility  in  35%  of  couples.  Causes  of  female  infertility  include  ovulatory  disorders,  chromosomal  abnormalities,  endometriosis,  pelvic  adhesions,  tubal  blockage  and  other  tubal  abnormalities,  and  hyperprolactinemia.  There  is  growing  evidence  that  genetic  abnormalities  are  present  in  as  many  as  10%  of  infertile  females  and  15%  of  infertile  males.  There  is  also  evidence  to  suggest  that  chromosomal  abnormalities  and  single  gene  mutations  contribute  to  the  cause  of  infertility  in  a  proportion  of  couples  seeking  infertility  therapy.  In  2002  the  Italian  community  of  professionals  working  in  reproductive  medicine  sought  to  set  out  guidelines  for  the  appropriate  use  of  genetic  testing  in  infertile  couples.Differential  diagnosis:Genetic  causes  of  female  infertility  include  ovulatory  disorders  such  as  Kallmann  syndrome,  fragile  X  syndrome,  as  well  as  karyotype  abnormalities,  and  primary  ciliary  dyskinesia.  Infertility  can  also  be  noted  as  a  minor  manifestation  in  many  other  genetic  conditions  including  galactosemia,  mucopolysaccharidosis,  Prader-Willi,  cystic  fibrosis,  pseudohypoparathyroidism  type  1a,  progressive  external  ophthalmoplegia,  autoimmune  polyglandular  syndrome  type  I,  ovarian  leukodystrophy,  ataxia  telangiectasia,  Demirhan  syndrome,  and  blepharophimosis-ptosis-epicanthus  inversus  syndrome.Monogenic  forms:In  addition  to  the  single  gene  defects  noted  earlier,  additional  rare  genetic  abnormalities  have  been  identified  in  infertile  women.  These  include  mutations  in  the  follicle-stimulating  hormone  (FSH),  luteinizing-hormone  (LH),  and  gonadotropin-releasing  hormone  (GnRH)  receptors,  and  mutations  in  the  androgen  receptor  causing  androgen  insensitivity  syndrome.Family  history:A  three-generation  pedigree  for  genetic  disorders  should  be  obtained  from  any  patient  who  is  undergoing  evaluation  or  treatment  for  infertility.  A  family  history  of  males  or  females  with  intellectual  disability  may  indicate  transmission  of  fragile  X  syndrome,  and  testing  for  this  disorder  is  indicated.Twin  studies:Twin  studies  have  demonstrated  a  greater  concordance  between  monozygotic  than  dizygotic  twins  in  reference  to  age  of  menopause.  The  prevalence  of  premature  ovarian  failure  is  three-  to  fivefold  greater  in  both  monozygotic  and  dizygotic  twins.  There  are  reports  in  the  literature  of  “ovarian  discordancy”  in  monozygotic  twins,  and  also  of  sister  →  sister  ovarian  tissue  transplantation  in  these  cases.Genome-wide  associations:Genome-wide  association  studies  (GWASs)  have  been  used  to  elucidate  the  genetic  etiology  of  premature  ovarian  failure.  Candidate  genes  have  been  identified;  however,  the  small  size  of  these  studies  has  limited  the  statistical  power  of  their  results.  Array  comparative  genomic  hybridization  (a-CGH)  analysis  is  also  being  researched  on  cohorts  of  women  with  premature  ovarian  failure  for  analysis  of  copy  number  variants  (CNVs)  over  the  genome.  A  number  of  potential  candidate  genes  including  PTHB1  and  ADAMTS19  have  been  identified  in  this  fashion,  although  larger  follow-up  studies  are  needed  to  confirm  these  findings.  
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/18
UR  - accessmedicine.mhmedical.com/content.aspx?aid=1102703880
ER  -