Details of Disease

General Information of Disease (ID: DISAMOWP)

• Disease Name: Infertility
• Synonyms: infertility; sterile; sterility; Sterile; fertility disorders; infertile
• Disease Class: GB04: Male infertility
• Definition: Inability to conceive for at least one year after trying and having unprotected sex. Causes of female infertility include endometriosis, fallopian tubes obstruction, and polycystic ovary syndrome. Causes of male infertility include abnormal sperm production or function, blockage of the epididymis, blockage of the ejaculatory ducts, hypospadias, exposure to pesticides, and health related issues.|Editor note: dubious as to whether this is a disease as defined, check with clingen before obsoleting
• Disease Hierarchy:
  DIS7W23Z: Reproductive system disorder
  DISAMOWP: Infertility
• ICD Code:
  ICD-11: ICD-11: GB04
  ICD-10: ICD-10: N46
• Disease Identifiers:
  MONDO ID: MONDO_0005047
  MESH ID: D007246
  UMLS CUI: C0021359
  MedGen ID: 43876
  HPO ID: HP:0000789
  SNOMED CT ID: 8619003

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 7 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Corifollitropin alfa	DMAG519	Approved	NA	[1]
Cyclofenil	DMT5RMB	Approved	Small molecular drug	[1]
Estradiol	DMUNTE3	Approved	Small molecular drug	[2]
Folic Acid	DMEMBJC	Approved	Small molecular drug	[3]
Idursulfase	DM30SXV	Approved	NA	[4]
Rfsh/rhfsh	DM6UC4C	Approved	NA	[1]
Triptorelin	DMTK4LS	Approved	Small molecular drug	[5]

This Disease is Treated as An Indication in 5 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
13-cis-retinoic acid	DMTZ1A5	Phase 3	NA	[6]
Follicle stimulating hormone	DMJNO3D	Phase 2	NA	[7]
Emfilermin	DMIOUFK	Phase 1/2	NA	[8]
FSH patch	DMIX1CA	Phase 1	NA	[9]
Org-43902	DME0WX2	Phase 1	NA	[10]

This Disease is Treated as An Indication in 1 Discontinued Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
PV903	DM90JMD	Discontinued in Phase 1	NA	[11]

This Disease is Treated as An Indication in 1 Investigative Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
V1A F/U	DMH971B	Investigative	NA	[12]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 8 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ATM	TTKBM7V	moderate	Biomarker	[13]
BRCA2	TTUARD6	moderate	Biomarker	[14]
ESR1	TTZAYWL	moderate	Biomarker	[15]
EHMT2	TTS6RZT	Strong	Biomarker	[16]
LEPR	TT0HD6V	Strong	Biomarker	[17]
PTGER2	TT1ZAVI	Strong	Biomarker	[18]
CFI	TT6ATLX	Definitive	Altered Expression	[19]
IL1R2	TT51DEV	Definitive	Altered Expression	[20]

This Disease Is Related to 7 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
IFT140	OT6KO5FH	Limited	CausalMutation	[21]
ADGRG2	OTPAD5S1	Strong	CausalMutation	[22]
KL	OTD4VWU6	Strong	Biomarker	[23]
TTC19	OTQ0QH1P	Strong	Biomarker	[24]
C9	OT7I5FDX	Definitive	Altered Expression	[19]
NLRP5	OTLU1YML	Definitive	Biomarker	[25]
TRO	OTRZQMU8	Definitive	Altered Expression	[26]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] Estradiol FDA Label
• [3] Folic acid FDA Label
• [4] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [5] Triptorelin FDA Label
• [6] ClinicalTrials.gov (NCT03323801) RA-4: 13-cis Retinoic Acid for Treatment of Men With Azoospermia. U.S. National Institutes of Health.
• [7] ClinicalTrials.gov (NCT01794208) Efficacy and Safety of FSH-GEX in Comparison With 150 IU Gonal-f. U.S. National Institutes of Health.
• [8] ClinicalTrials.gov (NCT00504530) r-hLIF for Improving Embryo Implantation in IVF. U.S. National Institutes of Health.
• [9] Clinical pipeline report, company report or official report of Pantec Biosolutions AG.
• [10] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800042073)
• [11] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020003)
• [12] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 366).
• [13] Rats with a missense mutation in Atm display neuroinflammation and neurodegeneration subsequent to accumulation of cytosolic DNA following unrepaired DNA damage.J Leukoc Biol. 2017 Apr;101(4):927-947. doi: 10.1189/jlb.4VMA0716-316R. Epub 2016 Nov 28.
• [14] Production of knockout rats using ENU mutagenesis and a yeast-based screening assay.Nat Biotechnol. 2003 Jun;21(6):645-51. doi: 10.1038/nbt830. Epub 2003 May 18.
• [15] Generation of Esr1-knockout rats using zinc finger nuclease-mediated genome editing.Endocrinology. 2014 May;155(5):1991-9. doi: 10.1210/en.2013-2150. Epub 2014 Feb 7.
• [16] Pubertal exposure to di-(2-ethylhexyl)-phthalate inhibits G9a-mediated histone methylation during spermatogenesis in mice.Arch Toxicol. 2016 Apr;90(4):955-69. doi: 10.1007/s00204-015-1529-2. Epub 2015 May 15.
• [17] Neuropeptidergic characterization of the leptin receptor mutated obese Koletsky rat.Regul Pept. 2004 Jun 15;119(1-2):3-10. doi: 10.1016/j.regpep.2003.12.016.
• [18] Reproductive failure and reduced blood pressure in mice lacking the EP2 prostaglandin E2 receptor.J Clin Invest. 1999 Jun;103(11):1539-45. doi: 10.1172/JCI6579.
• [19] Levels of complement components iC3b, C3c, C4, and SC5b-9 in peritoneal fluid and serum of infertile women with endometriosis.Fertil Steril. 2007 Nov;88(5):1298-303. doi: 10.1016/j.fertnstert.2006.12.061. Epub 2007 May 4.
• [20] Imbalance in the peritoneal levels of interleukin 1 and its decoy inhibitory receptor type II in endometriosis women with infertility and pelvic pain.Fertil Steril. 2008 Jun;89(6):1618-24. doi: 10.1016/j.fertnstert.2007.06.019. Epub 2007 Oct 24.
• [21] Impact of whole exome sequencing among Iranian patients with autosomal recessive retinitis pigmentosa.Arch Iran Med. 2015 Nov;18(11):776-85.
• [22] Truncating Mutations in the Adhesion G Protein-Coupled Receptor G2 Gene ADGRG2 Cause an X-Linked Congenital Bilateral Absence of Vas Deferens. Am J Hum Genet. 2016 Aug 4;99(2):437-42. doi: 10.1016/j.ajhg.2016.06.012. Epub 2016 Jul 28.
• [23] Mutation of the mouse klotho gene leads to a syndrome resembling ageing.Nature. 1997 Nov 6;390(6655):45-51. doi: 10.1038/36285.
• [24] Mutations in TTC19 cause mitochondrial complex III deficiency and neurological impairment in humans and flies. Nat Genet. 2011 Mar;43(3):259-63. doi: 10.1038/ng.761. Epub 2011 Jan 30.
• [25] A human homologue of mouse Mater, a maternal effect gene essential for early embryonic development.Hum Reprod. 2002 Apr;17(4):903-11. doi: 10.1093/humrep/17.4.903.
• [26] Expression of trophinin in the cycling endometrium and its association with infertility.Di Yi Jun Yi Da Xue Xue Bao. 2002 Jun;22(6):539-41.