Details of Disease

General Information of Disease (ID: DIS9GNYZ)

• Disease Name: Female infertility
• Synonyms: sub fertility, female; sterility, female; female sub-fertility; sterility, postpartum; female subfertility; female sterility; subfertility, female; postpartum sterility; sub-fertility, female; infertility disorder of female reproductive system; female reproductive system infertility; female reproductive system infertility disorder; female infertility
• Disease Class: GA31: Female infertility
• Definition: Diminished or absent ability of a female to achieve conception.
• Disease Hierarchy:
  DISAMOWP: Infertility
  DISXEPZF: Gynecological disease
  DIS9GNYZ: Female infertility
• ICD Code:
  ICD-11: ICD-11: GA31.Z
  ICD-9: ICD-9: 628
  Expand ICD-11: 'GA31
  Expand ICD-10: 'N97; 'N97.0; 'N97.3; 'N97.4; 'N97.8; 'N97.9
  Expand ICD-9: 628
• Disease Identifiers:
  MONDO ID: MONDO_0021124
  UMLS CUI: C0021361
  MedGen ID: 5795
  HPO ID: HP:0008222
  SNOMED CT ID: 6738008

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 8 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Albunex	DMXOQPZ	Approved	NA	[1]
Choriogonadotropin alfa	DMFMZ3G	Approved	NA	[2]
Clomifene	DMKI7RB	Approved	Small molecular drug	[3]
Clomiphene Citrate	DMS51VC	Approved	Small molecular drug	[1]
Follitropin beta	DM2JTS5	Approved	NA	[2]
Lutropin alfa	DM7K5GD	Approved	NA	[2]
Menotropins	DM4CF18	Approved	NA	[4]
Urofollitropin	DMG9HIA	Approved	Small molecular drug	[2]

This Disease is Treated as An Indication in 3 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
GnRH	DM0LQ94	Phase 3	NA	[5]
R-TPR-013	DMDB1YG	Phase 3	NA	[6]
AKP-501	DM9JU8L	Phase 1	NA	[7]

This Disease is Treated as An Indication in 2 Discontinued Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
PGL-3001	DMPSMBC	Discontinued in Phase 2	NA	[8]
GA-FSH	DMIYVJ2	Terminated	Small molecular drug	[9]

This Disease is Treated as An Indication in 4 Investigative Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Long-acting FSH conjugate	DMD32IN	Investigative	NA	[10]
PGL-1001	DMDAKD6	Investigative	NA	[11]
PRX-111	DMSPH30	Investigative	NA	[12]
Recombinant follicle stimulating hormone	DMNHOI3	Investigative	NA	[10]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 20 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
AR	TTKPW01	moderate	Biomarker	[13]
CCN2	TTIL516	moderate	Biomarker	[14]
CEBPA	TT5LWG1	moderate	Biomarker	[15]
CEBPB	TTUI35N	moderate	Biomarker	[15]
DHFR	TTYZVDJ	moderate	Therapeutic	[16]
ESR1	TTZAYWL	moderate	Biomarker	[13]
ESR2	TTOM3J0	moderate	Biomarker	[13]
FSHB	TT13GFV	moderate	Biomarker	[17]
LEP	TTBJEZ5	moderate	Biomarker	[18]
LEPR	TT0HD6V	moderate	Biomarker	[18]
LIF	TTGZ5WN	moderate	Biomarker	[19]
MAPK1	TT4TQBX	moderate	Biomarker	[15]
MAPK3	TT1MG9E	moderate	Biomarker	[15]
NR1I2	TT7LCTF	moderate	Biomarker	[13]
NR5A2	TTAU3SY	moderate	Biomarker	[20]
PRL	TTJ2TSA	moderate	Biomarker	[21]
SMO	TT8J1S3	moderate	Biomarker	[22]
CACNA2D2	TTU8P3M	Strong	Biomarker	[23]
CYP17A1	TTRA5BZ	Strong	Biomarker	[24]
CYP19A1	TTSZLWK	Strong	Biomarker	[25]

This Disease Is Related to 6 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ADIPOR1	OT65ZFZN	moderate	Biomarker	[18]
ADIPOR2	OT2HDTL8	moderate	Biomarker	[18]
BTG4	OTT3TKPI	Moderate	Autosomal recessive	[26]
LHB	OT5GBOVJ	moderate	Biomarker	[27]
NR2F2	OTJFS67N	moderate	Biomarker	[28]
PAPPA	OTTTG9PG	moderate	Biomarker	[29]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [3] 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. (Ligand id: 7619).
• [4] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 020328.
• [5] Clinical pipeline report, company report or official report of Ferring Pharmaceuticals Inc.
• [6] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032740)
• [7] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800030871)
• [8] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026645)
• [9] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021023)
• [10] 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: 253).
• [11] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [12] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800028182)
• [13] Correlation of endocrine disrupting chemicals serum levels and white blood cells gene expression of nuclear receptors in a population of infertile women.Int J Endocrinol. 2013;2013:510703. doi: 10.1155/2013/510703. Epub 2013 Apr 21.
• [14] Connective tissue growth factor is required for normal follicle development and ovulation.Mol Endocrinol. 2011 Oct;25(10):1740-59. doi: 10.1210/me.2011-1045. Epub 2011 Aug 25.
• [15] CCAAT/enhancer-binding proteins (C/EBP)- and - are essential for ovulation, luteinization, and the expression of key target genes.Mol Endocrinol. 2011 Feb;25(2):253-68. doi: 10.1210/me.2010-0318. Epub 2010 Dec 22.
• [16] Transgenic rescue of methotrexate-induced teratogenicity in Drosophila melanogaster.Toxicol Sci. 2007 Oct;99(2):522-31. doi: 10.1093/toxsci/kfm123. Epub 2007 May 22.
• [17] Primary amenorrhoea and infertility due to a mutation in the beta-subunit of follicle-stimulating hormone.Nat Genet. 1993 Sep;5(1):83-6. doi: 10.1038/ng0993-83.
• [18] Adiponectin and leptin systems in human endometrium during window of implantation.Fertil Steril. 2012 Mar;97(3):771-8.e1. doi: 10.1016/j.fertnstert.2011.12.042. Epub 2012 Jan 21.
• [19] Endometrial glands are essential for blastocyst implantation and decidualization in the mouse uterus.Biol Reprod. 2013 Apr 11;88(4):93. doi: 10.1095/biolreprod.113.107631. Print 2013 Apr.
• [20] Impaired progesterone production in Nr5a2+/- mice leads to a reduction in female reproductive function.Biol Reprod. 2007 Aug;77(2):217-25. doi: 10.1095/biolreprod.106.059121. Epub 2007 Apr 4.
• [21] Prolactin independent rescue of mouse corpus luteum life span: identification of prolactin and luteinizing hormone target genes.Am J Physiol Endocrinol Metab. 2009 Sep;297(3):E676-84. doi: 10.1152/ajpendo.91020.2008. Epub 2009 Jun 16.
• [22] Conditional loss of hepatocellular Hedgehog signaling in female mice leads to the persistence of hepatic steroidogenesis, androgenization and infertility.Arch Toxicol. 2017 Nov;91(11):3677-3687. doi: 10.1007/s00204-017-1999-5. Epub 2017 May 30.
• [23] entla, a novel epileptic and ataxic Cacna2d2 mutant of the mouse.J Biol Chem. 2004 Feb 20;279(8):7322-30. doi: 10.1074/jbc.M308778200. Epub 2003 Dec 2.
• [24] Partial 17alpha-hydroxylase/17,20-lyase deficiency-clinical report of five Chinese 46,XX cases. Gynecol Endocrinol. 2008 Jul;24(7):362-7. doi: 10.1080/09513590802194051.
• [25] Aromatase-knockout mouse carrying an estrogen-inducible enhanced green fluorescent protein gene facilitates detection of estrogen actions in vivo.Endocrinology. 2004 Apr;145(4):1880-8. doi: 10.1210/en.2003-0952. Epub 2003 Dec 18.
• [26] Homozygous Mutations in BTG4 Cause Zygotic Cleavage Failure and Female Infertility. Am J Hum Genet. 2020 Jul 2;107(1):24-33. doi: 10.1016/j.ajhg.2020.05.010. Epub 2020 Jun 4.
• [27] A new molecular variant of luteinizing hormone associated with female infertility.Fertil Steril. 1998 Jan;69(1):102-6. doi: 10.1016/s0015-0282(97)00445-7.
• [28] COUP-TFII mediates progesterone regulation of uterine implantation by controlling ER activity.PLoS Genet. 2007 Jun;3(6):e102. doi: 10.1371/journal.pgen.0030102.
• [29] Lack of functional pregnancy-associated plasma protein-A (PAPPA) compromises mouse ovarian steroidogenesis and female fertility.Biol Reprod. 2010 Jun;82(6):1129-38. doi: 10.1095/biolreprod.109.079517. Epub 2010 Feb 3.