Urofollitropin

Ferring Pharmaceuticals Reports Landmark Infertility Study Results at American Society for Reproductive Medicine Annual Meeting

MONTREAL, Oct. 17 /PRNewswire/ -- Ferring Pharmaceuticals today presented the results of a landmark clinical trial -- the largest in vitro fertilization (IVF) trial powered on pregnancy rates ever undertaken in infertility. Trial results determined predictors for successful outcomes and were presented at the 61st Annual Meeting of the American Society for Reproductive Medicine (ASRM) in Montreal, Quebec, Canada, October 15 - 19, 2005. A total of five poster presentations and two oral presentations offered during the meeting represented findings from this prospective, multicenter, multinational trial, Menotropins versus Recombinant FSH In Vitro Fertilization Trial (MERiT). A total of 731 women underwent controlled ovarian hyperstimulation (COH) following gonadotropin-releasing hormone (GnRH) agonist down-regulation in a long treatment protocol.

"The state-of-the-art study design, innovative approach to embryo assessment and analysis of the intrafollicular endocrine environment offer the most comprehensive evaluation of predictive measures for successful IVF outcomes ever undertaken," said Kenneth B. Kashkin, M.D., vice president, medical and regulatory affairs, Ferring Pharmaceuticals Inc. "This study provides the infertility community with more clinically relevant information than ever before to help physicians understand the physiological differences that result from treatment with human menopausal gonadotropin (hMG), which contains both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) activity, versus recombinant FSH only."

Beneficial influence of LH activity

The hormonal environment following treatment with either highly purified hMG (HP-hMG) (n=363) or recombinant FSH (follitropin alpha) (n=368) was examined to determine any differences in treatment. Levels of FSH, LH, human chorionic gonadotropin (hCG), androstenedione and estradiol detected in the follicular fluid were significantly higher (p<0.0001) among women stimulated with HP-hMG (MENOPUR(R) (menotropins for injection, USP)) compared to those treated with recombinant FSH (Gonal-f*). Follicular levels of progesterone were significantly higher (p<0.0001) in the recombinant FSH treatment group. The environment associated with gonadotropins containing LH activity (HP-hMG) is more estrogenic than androgenic or progestogenic compared to those without the activity (recombinant FSH). These distinct profiles may be relevant for interpreting differences in embryo quality parameters, which can affect pregnancy rates.

"As supported by recent studies, this data suggests that LH bioactivity may play an important role in successful IVF cycles," said Sandra A. Carson, M.D., professor of Obstetrics and Gynecology, Baylor College of Medicine. "This research also demonstrates differences in the endocrine environment in which oocytes develop. Additional research may be valuable to provide a better understanding of the impact of these differences on oocyte and embryo quality."

Predictors of ovarian response and ongoing pregnancy

Clinical, sonographic and endocrine parameters at baseline were examined to determine their value in predicting ovarian response and ongoing pregnancy in an IVF cycle. Study results demonstrated that increasing age (OR, 95% CI: 1.14, 1.03-1.25), short menstrual cycle duration (OR, 95% CI: 0.71, 0.60- 0.85), increasing total testosterone (OR, 95% CI: 1.89, 1.09-3.40) and low antral follicle count (OR, 95% CI: 0.90, 0.85-0.95) predict poor ovarian response. Type of gonadotropin preparation did not predict poor ovarian response.

Age, as well as primary cause and duration of infertility, were significant predictors of ongoing pregnancy. Endometrial thickness, serum total testosterone and duration of GnRH agonist prior to stimulation were also significant predictors. Women less than or equal to 29 and 30-34 years of age demonstrated an increased chance of pregnancy compared to women aged 35-37, with an odds ratio of 2.71 (95% CI: 1.46-5.32) and 2.40 (95% CI: 1.33-4.62), respectively. Mild male or tubal factor resulted in a decreased chance of ongoing pregnancy with an odds ratios of 0.40 (95% CI: 0.20-0.75) and 0.59 (95% CI: 0.40-0.88), respectively, compared to unexplained infertility.

Embryo quality parameters that independently predict ongoing pregnancy were also examined. Three significant (p<0.05) independent predictors of ongoing pregnancy were identified: cell number and blastomere (ball of cells resulting from repeated cleavage of fertilized egg) uniformity at 44 hours and cell number at 68 hours post-insemination when transferring embryos on treatment day three.

Early cleavage (series of cell divisions that changes the single-cell zygote into a multicellular embryo) was examined to see if it improves the ongoing pregnancy rate. Embryos that reached the two-cell stage at 28 hours post-insemination were found to have a significantly higher chance of developing into top quality embryos. Early cleavage was not found to increase pregnancy rates when transferring top quality embryos on treatment day three but did dramatically increase the pregnancy rates when the embryo transferred was not of top quality (set by previously determined factors).

Innovative approach to embryo assessment

In an analysis of all embryos, inter- and intraobserver agreement among embryologists was assessed when implementing a centralized evaluation of embryo quality. Embryos were evaluated by the embryologist at the local clinic, as well as centrally by a panel of three embryologists blinded to treatment (three separate analyses on each embryo) to minimize variability in embryo quality assessments. The study demonstrated a high level of inter- and intraobserver agreement on embryo quality parameters demonstrating that a combination of local and centralized evaluation is the most effective and reliable approach to determining embryo quality for large multicenter trials.

Clinical comparisons of HP-hMG and FSH (follitropin alpha)

A pooled analysis of two large, randomized, controlled clinical trials (MERiT (n=731) and EISG (n=727)) comparing HP-hMG (MENOPUR(R) (menotropins for injection, USP)) and recombinant FSH (Gonal-f) was conducted to provide an estimate of treatment differences between the two agents. The analysis showed that MENOPUR(R) resulted in significantly higher clinical (p=0.017) and ongoing pregnancy (p=0.030) rates than Gonal-f in IVF cycles.

In a separate analysis of 184 women with World Health Organization (WHO) Group II anovulatory infertility who failed to ovulate or conceive on clomiphene citrate and were randomized to receive either MENOPUR(R) or Gonal-f treatment in a low-dose step-up protocol, results demonstrated that treatment with MENOPUR(R) is associated with equivalent ovulation and pregnancy rates compared with Gonal-f.

MENOPUR(R), like all gonadotropins, is a potent substance capable of causing mild to severe adverse reactions, including ovarian hyperstimulation syndrome (OHSS) (incidence of 3.8%), with or without pulmonary or vascular complications, in women undergoing therapy for infertility. Only physicians thoroughly familiar with infertility treatment, including the risk of multiple births and adverse reactions, should prescribe this medication. The most common side effects are headache, abdominal pain and nausea.

About Ferring Pharmaceuticals Inc.

Ferring Pharmaceuticals Inc., part of the Ferring Group, is a privately owned, international pharmaceutical company. Ferring markets MENOPUR(R), BRAVELLE(R) (urofollitropin for injection, purified), REPRONEX(R) (menotropins for injection, USP) and NOVAREL(R) (chorionic gonadotropin for injection, USP) in the U.S. to infertility specialists and their patients. Ferring also offers the Q-CAP(TM), the first and only needle-free reconstitution device, for use with its fertility treatments.

The Ferring Group specializes in the research, development and commercialization of compounds in general and pediatric endocrinology, urology, gastroenterology, obstetrics/gynecology and infertility. For more information, visit http://www.ferringfertility.com/ or http://www.ferringusa.com/.

* Gonal-f is a registered trademark of Serono.

CONTACT: Kelly Laban, Kovak-Likly Communications, +1-203-762-8833 x15, KLaban@KLCpr.com, for Ferring Pharmaceuticals Inc.

Web site: http://www.ferringfertility.com/ http://www.ferringusa.com/

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