Urofollitropin
Follicle-stimulating hormone purified from the urine of post-menopausal women, the forerunner of recombinant FSH
Urofollitropin is FSH extracted and purified from the urine of post-menopausal women. In the US it was sold as Metrodin and Fertinex (approved 1986, discontinued) and later as Bravelle; recombinant FSH has largely replaced it, and no current US label could be read.
What is it?
Urinary FSH made IVF stimulation possible, and highly purified versions narrowed the gap with recombinant FSH. In the trials of the late 1990s, recombinant FSH still retrieved more eggs and embryos from fewer ampoules and days; one 2003 trial found Bravelle matched follitropin beta, with less painful injections.
Later trials closed the gap entirely on the outcome that matters. In 152 IVF patients randomised in 2009, highly purified urinary FSH and recombinant FSH retrieved about 16 to 17 eggs each and produced identical live birth rates of 38.2%. In ovulation induction for women with polycystic ovaries who did not respond to clomiphene, nearly all ovulated within three cycles on either, although recombinant FSH used less drug.
Urinary FSH also treats men. In 28 men whose pituitary made no gonadotropins, adding it to hCG for 18 months started sperm production in 89%, and in men with mildly small testes it was linked to better testosterone and sperm measures. A randomised study found it shifted clotting measures more than recombinant FSH during stimulation, a reminder that the products are not identical.
Products are not interchangeable: a 2012 systematic review found one human-derived FSH, Fostimon, outperformed another, Metrodin-HP, and warned against assuming all such products work alike. Drugs@FDA lists Metrodin and Fertinex as discontinued, one Bravelle application as discontinued and another still as prescription.
Mechanism of Action
Urofollitropin is follicle-stimulating hormone purified from human urine; it stimulates ovarian follicles and, in men, sperm production.
Follicle growth
Activates FSH receptors on ovarian granulosa cells, recruiting several follicles for IVF or ovulation induction.
Sperm production
With hCG, it acts on Sertoli cells to start and maintain spermatogenesis in men lacking gonadotropins.
Purity varies
Purity and consistency vary between products, and a systematic review found they are not interchangeable.
Published Research
Comparative trials, a quality study and two reviews read from their PubMed abstracts; no current US label could be read.
Against recombinant Gonal-F
Recombinant FSH needed fewer 75 IU ampoules than highly purified urinary FSH (21.9 against 31.9) and produced more embryos (8.1 against 4.7).
A second comparison
In a double-blind trial, recombinant FSH retrieved more oocytes (11.0 against 8.8) and embryos (5.1 against 3.5) than highly purified urinary FSH, over fewer days (11.7 against 14.5) and ampoules.
Bravelle against Follistim
Bravelle and follitropin beta had comparable efficacy in IVF stimulation and similar adverse events; patients reported Bravelle injections as significantly less painful.
Women over 37 having IVF
In 486 cycles in Chinese women over 37, highly purified urinary FSH gave higher fertilisation (87.4% against 76.6%) and top-grade embryo rates (49.8% against 40.8%) than recombinant FSH, with fewer cycles lacking a transferable embryo; pregnancy rates did not differ significantly.
Men with azoospermia before sperm retrieval
In 50 men with idiopathic azoospermia, those given urofollitropin before testicular sperm extraction had higher pregnancy (28% against 15%) and fertilisation rates than untreated men; 5 treated men had sperm in the ejaculate. The study was small.
Live births: no difference
In 152 IVF volunteers randomised at a 300 IU starting dose, highly purified urinary FSH and recombinant FSH retrieved similar oocyte numbers (16.3 against 17.1) and gave the same live birth rate, 38.2% in each group.
Ovulation induction in PCOS
In 172 women with clomiphene-resistant anovulation on a low-dose step-up regimen from 75 IU, cumulative ovulation after three cycles was 96% on urinary FSH and 95% on recombinant, but recombinant needed less drug and fewer days in the first cycle.
Three generations of urinary products
Across 238 IVF cycles with embryo transfer, clinical pregnancy rates per transfer in young women were similar with Pergonal plus Metrodin, Metrodin, Fertinex plus Pergonal and subcutaneous Fertinex alone.
Bravelle mixed with hMG
In women having IVF, three different ratios of Bravelle to hMG gave comparable implantation, pregnancy and take-home baby rates, with better results in women under 34.
Men with hypogonadotropic hypogonadism
In 28 men given hCG and then highly purified urinary FSH with hCG for 18 months, 89.3% began producing sperm and 64.3% reached at least 1.5 million per mL, without serious drug-related adverse events.
Men with smaller testes
In infertile men with mildly reduced testicular volume, those treated with urofollitropin had higher testosterone and better sperm counts and motility at follow-up than untreated men.
Effects on blood clotting
During stimulation, highly purified urinary FSH lowered antithrombin and t-PA and raised INR, while recombinant FSH changed fewer clotting measures, in a randomised comparison.
Not all urinary FSH is the same
A systematic review found Fostimon superior to Metrodin-HP on clinical outcomes, including pregnancy rates, with no difference in OHSS or miscarriage, and cautioned against assuming human-derived FSH products are equivalent.
Its place in ovulation induction
A review judged urofollitropin and recombinant FSH equally effective and well tolerated for ovulation induction, hMG comparable on pregnancy outcomes, and urinary FSH still useful where cost matters more than convenience.
Purity and consistency
A laboratory comparison found highly purified urofollitropin carried variable urine-derived contaminant proteins and variable FSH purity, isoforms and delivered dose, falling short of follitropin alfa's quality attributes.
Against FSH plus hMG
In standard IVF, purified urinary FSH (Metrodin HP) gave a higher pregnancy rate per started cycle than FSH combined with hMG (35% against 18%).
Dosing Data
The last US label, Bravelle's, started ovulation induction at 150 IU a day and ART at 225 IU a day, adjusted every two days or more, never above 450 IU or beyond 12 days. The product is now discontinued.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the trials.
Contraindications & Cautions
No current US label could be read.
Legal Status
US products discontinued or listed without a readable label.
Frequently Asked Questions
?Is urinary FSH still used?
Recombinant FSH has largely replaced it in the US; Drugs@FDA lists the Metrodin and Fertinex products as discontinued.
?Does it work as well as recombinant FSH?
In the 1997 and 2000 trials recombinant FSH gave more eggs and embryos from less drug; the 2003 Bravelle trial found comparable results.
?Are all urinary FSH products the same?
No: a 2012 systematic review found clinically different results between two human-derived products.
?Is Bravelle still sold?
Drugs@FDA lists one Bravelle application as discontinued and another still as prescription; no current Bravelle label could be read on DailyMed.
References
- [clinical-trial] Bergh C, et al. "Recombinant human follicle stimulating hormone (r-hFSH; Gonal-F) versus highly purified urinary FSH (Metrodin HP): results of a randomized comparative study in women undergoing assisted reproductive techniques." Hum Reprod, 1997;12(10):2133-9. PMID: 9402268.
- [clinical-trial] Frydman R, et al. "A double-blind, randomized study to compare recombinant human follicle stimulating hormone (FSH; Gonal-F) with highly purified urinary FSH (Metrodin) HP) in women undergoing assisted reproductive techniques including intracytoplasmic sperm injection. The French Multicentre Trialists." Hum Reprod, 2000;15(3):520-5. PMID: 10686190.
- [clinical-trial] Dickey RP, et al. "Highly purified human-derived follicle-stimulating hormone (Bravelle) has equivalent efficacy to follitropin-beta (Follistim) in infertile women undergoing in vitro fertilization." Reprod Biol Endocrinol, 2003;1:63. PMID: 14609434.
- [review] Al-Inany HG, et al. "Are all human-derived follicle-stimulating hormone products the same? A systematic review and meta-analysis using direct and adjusted indirect analyses, to determine whether Fostimon® is more efficient than Metrodin-HP®." Gynecol Endocrinol, 2012;28(2):94-101. PMID: 21591977.
- [review] van Wely M, et al. "Urofollitropin and ovulation induction." Treat Endocrinol, 2005;4(3):155-65. PMID: 15898821.
- [pubmed] Lispi M, et al. "Comparative assessment of the consistency and quality of a highly purified FSH extracted from human urine (urofollitropin) and a recombinant human FSH (follitropin alpha)." Reprod Biomed Online, 2006;13(2):179-93. PMID: 16895630.
- [clinical-trial] Wikland M, et al. "Results from in vitro fertilization and intracytoplasmic sperm injection with purified gonadotrophins (Metrodin HP)." Horm Res, 1995;43(5):238-40. PMID: 7782057.
- [pubmed] Liu X, et al. "Efficacy of Highly Purified Urinary FSH versus Recombinant FSH in Chinese Women over 37 Years Undergoing Assisted Reproductive Techniques." Int J Fertil Steril, 2015;8(4):385-92. PMID: 25780520.
- [pubmed] Cocci A, et al. "Effectiveness of highly purified urofollitropin treatment in patients with idiopathic azoospermia before testicular sperm extraction." Urologia, 2018;85(1):19-21. PMID: 28799634.
- [pubmed] Baker VL, et al. "Clinical efficacy of highly purified urinary FSH versus recombinant FSH in volunteers undergoing controlled ovarian stimulation for in vitro fertilization: a randomized, multicenter, investigator-blind trial." Fertil Steril, 2009;91(4):1005-11. PMID: 18367182.
- [pubmed] Coelingh Bennink HJ, et al. "Recombinant follicle-stimulating hormone (FSH; Puregon) is more efficient than urinary FSH (Metrodin) in women with clomiphene citrate-resistant, normogonadotropic, chronic anovulation: a prospective, multicenter, assessor-blind, randomized, clinical trial. European Puregon Collaborative Anovulation Study Group." Fertil Steril, 1998;69(1):19-25. PMID: 9457926.
- [pubmed] Crain JL, et al. "Outcome comparison of in vitro fertilization treatment with highly purified subcutaneous follicle-stimulating hormone (Fertinex, a urofollitropin) versus intramuscular menotropins." Am J Obstet Gynecol, 1998;179(2):299-307. PMID: 9731830.
- [pubmed] Keye WR Jr, et al. "Evaluation of mixed protocols with Bravelle (human-derived FSH) and Repronex (hMG) to assess clinical efficacy (EMBRACE) in women undergoing in vitro fertilization." Fertil Steril, 2004;82(2):348-57. PMID: 15302283.
- [pubmed] "Efficacy and safety of highly purified urinary follicle-stimulating hormone with human chorionic gonadotropin for treating men with isolated hypogonadotropic hypogonadism. European Metrodin HP Study Group." Fertil Steril, 1998;70(2):256-62. PMID: 9696217.
- [pubmed] La Vignera S, et al. "Testosterone levels after treatment with urofollitropin in infertile patients with idiopathic mild reduction of testicular volume." Endocrine, 2019;66(2):381-385. PMID: 31240459.
- [pubmed] Ricci G, et al. "Impact of highly purified urinary FSH and recombinant FSH on haemostasis: an open-label, randomized, controlled trial." Hum Reprod, 2004;19(4):838-48. PMID: 15016779.
Sources & Citations
Studies were read from their PubMed abstracts; the Bravelle label (revised February 2014) was read on Drugs@FDA October 7, 2026. DailyMed carries no current urofollitropin label.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.