Gonadotropin preparations

Gonadotropin preparations are drugs that mimic the physiological effects of gonadotropins, used therapeutically mainly as fertility medication. For example, the so called menotropins consist of LH and FSH extracted from human urine from menopausal women.[1] There are also recombinant variants.

Contents

FSH and LH Preparations

hMG (human Menopausal Gonadotrophins), FSH and LH prepared from human urine collected from postmenopausal women. First extracted in 1953.[2] Injected intra-muscularily (IM) or subcutaneously (SC).

Generic

menotropins for injections, USP

Brands

  • Menopur, 5 mL vials containing 75 IU FSH and 75 IU LH.
  • Repronex, vials containing either 75 IU FSH and 75 IU LH, or 150 IU FSH and 150 IU LH.

FSH Preparations

There are two types of FSH preparations. Those derived from the urine of menopausal women and recombinant preparations. The recombinant preparations are more pure and more easily administered, but they are more expensive. The urinary preparations are equally effective and less expensive, but are not as convenient to administer as they are available in vials versus injection pens. One study reported that users of the purified urinary FSH preparation Bravelle experienced less injection stite pain compared to the recombinant preparation Follistim.[3]

Urinary Preparations

Purified urinary FSH (75 IU FSH and ≤ 2 IU of LH)
Generic
urofollitropin for injection, purified.
Brands
  • Bravelle, U.S., (≤ 2 IU LH)
  • Metrodin, U.S. and Canada, (≤ 1 IU LH)
  • Fertinorm Hp, (Canada)
Highly purified urinary FSH (75 IU FSH and ≤ 0.1 IU LH/1000 IU FSH)
Generic
urofollitropin for injection, (highly) purified.
Dosage
typically 75 - 300, but as high as 600 IU / day
Brands
Fertinex (≤ 0.1 IU LH/1000 IU FSH)

Recombinant Preparations

Follitropin alfa
Generic
Follitropin alfa injection
Brands
Gonal-F
Follitropin beta
Generic
follitropin beta injection
Brands
  • Follistim
  • Puregon

The package insert for Gonal-F states that based on physio-chemical tests and bioassays that follitropin beta and follitropin alfa are indistinguishable. Two studies showed no difference.[4][5] However, a more recent study showed there is may be a slight clinical difference, with the alfa form tending towards a higher pregnancy rate and the beta form tending towards a lower pregnancy rate, but with significantly higher estradiol (E2) levels.[6]

The package insert for Puregon states that structural analysis shows that the amino acid sequence of follitropin beta is identical to that of natural human follicle stimulating hormone (hFSH). Further, the ogliosaccharide side chains are very similar, but not completely identical to that of natural hFSH. However, these small differences do not affect the bioactivity compared to natural hFSH.

FSH Analogs

Corifollitropin alfa

Merck received approval on February 15, 2010 from the European Commission for ELONVA (corifollitropin alfa) a long lasting single injection fusion protein lacking LH activity. Only one injection is required for the first seven days, replacing the first seven daily injections of conventional FSH. Initial results demonstrates similar pregnancy rates as daily recombinant FSH injections.[7][8]

LH (Luteinizing hormone) Preparations

Prepared from recombinant DNA.

Generic
lutropin alfa for injection
Brands
Luveris

hCG (human Chorionic Gonadotropin) Preparations

Used to induce final maturation of follicle and subsequent ovulation. Also used for luteal phase support. Typically a single injection of 10,000 international units is used to induce ovulation. Recent data has shown that subcutaneous injection works as well as intramuscular injection, however this form of administration is not FDA approved.[9]

Urinary Preparations

Derived from the urine of pregnant women.

Generic
(human) chorionic gonadotropin for injection, USP
Brands
  • Pregnyl (Merck/Schering-Plough)
  • Follutein
  • Profasi
  • Novarel

Recombinant Preparations

Generic
choriogonadotropin alfa for injection (recombinant human Chorionic Gonadotropin, r-hCG).
Brands
Ovidrel

References

  1. ^ MeSH Menotropins
  2. ^ Ghumman, Surveen, 2006. Step by Step Ovulation Induction. Anshan Ltd, Kent, United Kingdom. ISBN 1-904798-96-9. Page 44.
  3. ^ Dickey RP, Thornton M, Nichols J, Marshall DC, Fein SH, Nardi RV. Comparison of the efficacy and safety of a highly purified human follicle-stimulating hormone (Bravelle) and recombinant follitropin-beta for in vitro fertilization: a prospective, randomized study. Fertility and Sterility 2002 Jun;77(6): 1202-8.
  4. ^ Peter Brinsden, Fidelis Akagbosu, Lisa M Gibbons, Susan Lancaster, Dominique Gourdon, Patrick Engrand, Ernest Loumaye, 2000. "A comparison of the efficacy and tolerability of two recombinant human follicle-stimulating hormone preparations in patients undergoing in vitro fertilization-embryo transfer." Fertility and sterility, 73(1): 114-116.
  5. ^ R. Stan Williams, et al., 2003. "Pregnancy rates in varying age groups after in vitro fertilization: a comparison of follitropin alfa (Gonal F) and follitropin beta (Follistim)." American Journal of Obstetrics and Gynecology, 189(2):342-346.
  6. ^ Orvieto R, Nahum R, Rabinson J, Ashkenazi J, Anteby EY, Meltcer S., 2009. "Follitropin-alpha (Gonal-F) versus follitropin-beta (Puregon) in controlled ovarian hyperstimulation for in vitro fertilization: is there any difference?" Fertility and Sterility 2009 Apr;91(4 Suppl):1522-5. Epub 2008 Oct 11. PMID 18851846
  7. ^ N. P. Koper, R. Boostanfar, P. Devroey, B. C. Fauser, P. C. IJzerman-Boon, B. M. J. L. Mannaerts. Global ClinicalDevelopment, Organon, Part of Schering-Plough Corporation, Oss, Netherlands; Huntington Reproductive Center, Tarzana, CA; Center of Reproductive Medicine, Dutch-speaking Free University, Brussels, Belgium; University Medical Center Utrecht, Utrecht, Netherlands; Biometrics, NV Organon, Part of Schering-Plough Corporation, Oss, Netherlands. "Corifollitropin alfa demonstrates similar pregnancy rates as compared to daily recombinant FSH treatment in a controlled ovarian stimulation regimen for IVF/ICSI." Fertility and Sterility, 90:page S75.
  8. ^ Devroey P, Boostanfar R, Koper NP, Mannaerts BM, Ijzerman-Boon PC, Fauser BC, 2009. "A double-blind, non-inferiority RCT comparing corifollitropin alfa and recombinant FSH during the first seven days of ovarian stimulation using a GnRH antagonist protocol." Human Reproduction, 2009, August 14, [Epub ahead of print]. PMID 19684043.
  9. ^ http://www.washivf.com/GWIVF-GWIVF_Content_C-Index_Page_Template_1143644788329.html
Gonadotropins and GnRH (G03G)
Gonadotropin
preparations
Agonist
Antigonadotropin
GnRH