Bye-bye urinary gonadotrophins?

The use of urinary gonadotrophins should be discouraged

Roberto Matorras,1 and Francisco J. Rodríguez-Escudero

Human Reproduction Unit, Hospital de Cruces, País Vasco University, Baracaldo, Vizcaya, Spain


    Abstract
 Top
 Abstract
 Introduction
 References
 
In view of concerns regarding the potential presence and infectivity of prion proteins in human urinary gonadotrophin preparations, together with the availability of both recombinant FSH and recombinant LH, it is argued that the use of urinary gonadotrophins should be discouraged.

Key words: BSE/new variant CJD/TSE/urinary gonadotrophins


    Introduction
 Top
 Abstract
 Introduction
 References
 
Transmissible spongiform encephalopathies (TSEs), or prion diseases, are fatal degenerative disorders of the central nervous system that affect humans and animals. Although some TSEs, like scrapie in sheep, have been known to exist for centuries, bovine spongiform encephalopathy (BSE) was recognized only 15 years ago (Glatzel and Aguzzi, 2001Go). New variant Creutzfeldt-Jakob disease (nvCJD) of humans is probably caused by consumption of BSE-infected materials (‘mad cow" disease). The nature of the infectious agent is not fully elucidated, but substantial evidence suggests that it is devoid of nucleic acids and consists at least in part of an abnormal form of a host protein termed PrP(C) (Glatzel and Aguzzi, 2001Go). Despite their rarity, prion diseases have become an important topic in public health and basic research because of the connection between nvCJD and BSE and also because of the unusual biological attributes of the infectious agent (Belay, 1999Go; Glatzel and Aguzzi, 2001Go).

It has been recently found that a prion protein isoform is present in urine of animals and humans affected with TSEs (Shaked et al., 2001Go). Most important, this prion protein was also found in the urine of hamsters inoculated with prions long before the appearance of clinical signs. However, this urinary prion protein failed to cause prion disease in hamsters when inoculated intracerebrally (Shaked et al., 2001Go).

Although infectivity by urine prions in humans or animals has not yet been documented, the aforementioned report raises serious concerns regarding the future use of urinary gonadotrophins. This is especially remarkable, since compared with recombinant FSH, urinary gonadotrophins have no evident clinical benefits (Daya and Gunby, 1999Go; Matorras et al., 2000Go), whereas cost-effectiveness studies did not reveal considerable advantages (Balasch and Barri, 2001Go). Indeed with the recent commercialization of recombinant LH, the LH administration recommended by some authors in any IVF treatment (Levy et al., 2000Go) can be obtained without using urinary gonadotrophins.

Thus, in our opinion, the use of urinary gonadotrophins should be discouraged.


    Notes
 
1 To whom correspondence should be addressed at: María Diaz de Haro 7, 6 iz, 48013 Bilbao, Spain. E-mail: rmatorras{at}hcru.osakidetza.net Back


    References
 Top
 Abstract
 Introduction
 References
 
Balasch, J. and Barri, P.N. (2001) Reflections on the cost-effectiveness of recombinant FSH in assisted reproduction. The clinician's perspective. J. Assist. Reprod. Genet., 18, 45–55.[ISI][Medline]

Belay, E.D. (1999) Transmissible spongiform encephalopathies in humans. Ann. Rev. Microbiol., 53, 283–314.[ISI][Medline]

Daya, S. and Gunby, J. (1999) Recombinant versus urinary follicle stimulating hormone for ovarian stimulation in assisted reproduction. Hum. Reprod., 14, 2207–2215.[Abstract/Free Full Text]

Glatzel, M. and Aguzzi, A. (2001) The shifting biology of prions. Brain Res. Rev., 36, 241–248.[ISI][Medline]

Levy, D.P., Navarro, J.M., Schattman, G.L., Davis, O.K. and Rosenwaks, Z. (2000) The role of LH in ovarian stimulation: exogenous LH: let's design the future. Hum. Reprod., 15, 2258–2265.[Abstract/Free Full Text]

Matorras, R., Recio, V., Corcóstegui, B. and Rodríguez-Escudero, F.J. (2000) Recombinant human FSH versus highly purified urinary FSH: a randomized study in intrauterine insemination with husbands' spermatozoa. Hum. Reprod., 15, 1231–1234.[Abstract/Free Full Text]

Shaked, G.M., Shaked, Y., Kariv-Inbal, Z., Halimi, M., Avraham, I. and Gabizon, R. (2001) A protease-resistant prion protein isoform is present in urine of animals and humans affected with prion diseases. J. Biol. Chem., 276, 31479–31482.[Abstract/Free Full Text]