Fertility medication

Fertility medication, better known as fertility drugs, are drugs which enhance reproductive fertility. For women, fertility medication is used to stimulate follicle development of the ovary. There are currently very few fertility medication options available for men.[1]

Agents that enhance ovarian activity can be classified as either Gonadotropin releasing hormone, Estrogen antagonists or Gonadotropins.

Female

Main techniques

The main techniques involving fertility medication in females are:

Gonadotropin-releasing hormone

Either Gonadotropin-releasing hormone (GnRH) or any Gonadotropin-releasing hormone agonist (i.e. Lupron) may be used. GnRH stimulates the release of gonadotropins (LH and FSH) from the anterior pituitary in the body.

Antiestrogens

Antiestrogens inhibit the effects of estrogen includes Clomiphene and Aromatase inhibitors.

Hypothalamic–pituitary–gonadal axis in females, with estrogen exerting mainly negative feedback on FSH secretion from the pituitary gland.

Clomiphene

Clomiphene (trademarked as Clomid) is a selective estrogen receptor modulator (SERM).[4] It is the most widely used fertility drug. It is used in ovulation induction by inhibiting the negative feedback of estrogen at the hypothalamus. As the negative feedback of estrogen is inhibited, the hypothalamus secretes GnRh which in turn stimulates the anterior pituitary to secrete LH and FSH which help in ovulation.

Aromatase inhibitors

Although primarily a breast cancer treatment, aromatase inhibitors are also used in ovulation induction, probably through a mechanism similar to clomiphene. Aromatase inhibitors will decrease the amount of testosterone converted to estradiol. Less estradiol circulating in the body will decrease the negative feedback at the level of the hypothalamus and result in sustained FSH secretion. More FSH will be available to stimulate the ovary and mature multiple follicles for ovulation. This is a common fertility treatment to treat women with PCOS.[5]

Gonadotropins

Gonadotropins are protein hormones that stimulate the gonads (testes and ovaries).[6] For medication, they can be extracted from urine or by genetic modification.

For example, the so-called menotropins consist of LH and FSH extracted from human urine from menopausal women.[7] There are also recombinant variants which are created by inserting the DNA coding for it into bacteriae. The bacterial DNA is then called Recombinant DNA. Examples of recombinant FSH are Follistim and Gonal F, while Luveris is a recombinant LH.

FSH and recombinant FSH analogues are mainly used for controlled ovarian hyperstimulation as well as ovulation induction.

Human chorionic gonadotropin

Human chorionic gonadotropin (hCG), also known as the “hormone of pregnancy” is a hormone that is normally produced during pregnancy and plays an integral role throughout reproduction.[8] It is crucial in maintaining pregnancy, from the stages of placentation through to early embryo development.[8] hCG is also used in assisted reproductive techniques as it can be used to replace Luteinizing Hormone (LH) in final maturation induction.[8]

Male

There currently are no effective medications to treat oligospermia, so other assisted reproductive technologies are used.

Adverse effects

The use of fertility drugs is highly correlated with other ovarian cancer risk factors which complicates the direct contribution of the fertility drugs to ovarian cancer. Numerous studies indicate the risk of developing ovarian cancer as a result of fertility drugs is insignificant, but long-term exposure to fertility drugs may require further studies to determine their role in ovarian tumors and other health risks.[9] Estrogen antagonists and gonadotropins may stimulate multiple follicles and other ovarian hormones leading to multiple birth and possible ovarian hyperstimulation syndrome.

Development of ovarian hyperstimulation syndrome (OHSS) is dependent on the administration of human chorionic gonadotropin (hCG) and is mediated through vascular endothelial growth factor (VEGF). OHSS is characterized as cystic enlargement of the ovaries.[10] Multiple birth is especially deleterious due to compounding risks including premature delivery and low birthweight, pre-eclampisa, and increased risk of neonatal mortality.[11] While triplet births have been declining in ART, multiple births remain over 50% of births from IVF. However, there are limitations to this date, as 4% to 8% IVF clinics to do not report their data to the CDC.[12]

See also

Manufacturers:

  • Ferring Pharmaceuticals
  • Organon International
  • EMD Serono

References

  1. Drobnis, Erma Z; Nangia, Ajay K (2017). Impacts of Medications on Male Fertility. Cham, Switzerland: Palgrave Macmillan. ISBN 978-3-319-69535-8. Retrieved 23 February 2019.
  2. Antral Follicle Counts, Resting Follicles, Ovarian Volume and Ovarian Reserve. Testing of egg supply and predicting response to ovarian stimulation drugs Advanced Fertility Center of Chicago. Retrieved on October 2, 2009
  3. Fertility: assessment and treatment for people with fertility problems. NICE clinical guideline CG156 - Issued: February 2013
  4. Stute, Petra; Birkhauser, Martin (2015). "Selective estrogen receptor modulators (SERM)/Selektive Ostrogenrezeptormodulatoren (SERM)". Gynakologische Endokrinologie. 13 (2): 126. doi:10.1007/s10304-015-0003-9.
  5. Badawy A, Abdel Aal I, Abulatta M (September 2009). "Clomiphene citrate or letrozole for ovulation induction in women with polycystic ovarian syndrome: a prospective randomized trial". Fertility and Sterility. 92 (3): 849–52. doi:10.1016/j.fertnstert.2007.02.062. PMID 17582406.
  6. Scwab, Manfred (2008). Encyclopedia of Cancer - Gonadatropins. Berlin, Heidelberg: Springer. ISBN 978-3-642-16483-5. Retrieved 23 February 2019.
  7. Menotropins at the US National Library of Medicine Medical Subject Headings (MeSH)
  8. Leão Rde B, Esteves SC (2014). "Gonadotropin therapy in assisted reproduction: an evolutionary perspective from biologics to biotech". Clinics (Sao Paulo, Brazil). 69 (4): 279–93. doi:10.6061/clinics/2014(04)10. PMC 3971356. PMID 24714837.
  9. Diergaarde B, Kurta ML (June 2014). "Use of fertility drugs and risk of ovarian cancer". Current Opinion in Obstetrics & Gynecology. 26 (3): 125–9. doi:10.1097/GCO.0000000000000060. PMC 4217689. PMID 24752005.
  10. Kumar P, Sait SF, Sharma A, Kumar M (May 2011). "Ovarian hyperstimulation syndrome". Journal of Human Reproductive Sciences. 4 (2): 70–5. doi:10.4103/0974-1208.86080. PMC 3205536. PMID 22065820.
  11. Workshop Group, T. E. C. (August 2000). "Multiple gestation pregnancy. The ESHRE Capri Workshop Group". Human Reproduction (Oxford, England). 15 (8): 1856–64. doi:10.1093/humrep/15.8.1856. PMID 10920117.
  12. Schieve LA, Peterson HB, Meikle SF, Jeng G, Danel I, Burnett NM, Wilcox LS (November 1999). "Live-birth rates and multiple-birth risk using in vitro fertilization". JAMA. 282 (19): 1832–8. doi:10.1001/jama.282.19.1832. PMID 10573274.
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