Dose-finding study of triptorelin acetate for prevention of a premature LH surge in IVF: a prospective, randomized, double-blind, placebo-controlled study

Abstract

Gonadotrophin-releasing hormone agonists (GnRHa) are routinely used in IVF programmes to prevent an unwanted LH surge and consequent ovulation. Despite its widespread use in IVF, a convincing dose recommendation for GnRHa in IVF does not exist. In our opinion, the lowest possible dose of GnRHa should be used. Thus, we performed a prospective, randomized, double-blind, placebo-controlled study to determine the minimal daily dose of triptorelin acetate needed to suppress a premature LH surge during IVF treatment in a long protocol. A total of 240 women (60 in each group) was randomized to either placebo or to one of three doses of triptorelin, i.e. 15, 50 or 100 microg daily. Ovarian stimulation was performed with two or three ampoules of FSH daily. A premature LH surge occurred in 23% of placebo-treated patients, but in none of the triptorelin acetate-treated patients. There were significantly more oocytes and embryos in the 50 and 100 microg triptorelin groups. There was no dose relationship in rates of either implantation, pregnancy, ongoing pregnancy, live birth or baby take-home. In this study we showed that daily administration of 15 microg triptorelin is sufficient to prevent a premature LH surge, and that 50 microg is equivalent to 100 microg in terms of IVF results.

Failure of the GnRH antagonist ganirelix to block the positive feedback effect of exogenous estrogen in normal women

“…Over the past 25 years, GnRH agonists have been used successfully to prevent a premature LH surge in IVF cycles (1,2). More recently, GnRH antagonists were introduced to simplify the protocols and reduce the cost of the IVF treatment, but it is still debatable whether they are equally effective as agonists regarding live birth rate (3).…”

Comparing stimulation requirements and final outcome between early follicular and mid luteal pituitary suppression in the long gonadotropin releasing hormone agonist protocol

“…Pellicer et al (1989) found that there was no difference between the two protocols regarding the dose of gonadotropins necessary to reach an optimal response, fertilization and cleavage rates. Three other studies performed by Pellicer et al (1989), Ron-El et al (1990) and Kondaveeti-Gordon et al (1996) reported that there was evidence of higher amounts of gonadotropins required in the luteal start (Janssens et al, 2000) In conclusion, the two timing of starting the agonist were sufficiently potent to produce pituitary suppression in a short period of time. Stimulation requirements as the number of gonadotropin vials and the days of stimulation required to reach the criteria of hCG administration were comparable in the two groups.…”

“…Such a benefit explained the marked improvement of IVF results associated with the introduction of its use. As shown by placebo-controlled studies on GnRH agonists, LH surges occur in 20% of IVF patients, leading to cancellation of the IVF cycles (Edwards et al, 1996;Janssens et al, 2000). There are three main protocols involving the administration of GnRH: short, ultrashort and long protocols.…”

A novel approach using a minimal number of injections during the IVF/ICSI cycle: Luteal half-dose depot GnRH agonist following corifollitropin alfa versus the corifollitropin alfa with a GnRH-antagonist cycle

“…Hesitation to use a depot agonist was related to the concern that it might lead to pituitary oversuppression, which could cause a luteal phase defect because of the absence of pituitary luteinizing hormone (10, 11). However, the use of halfdose depot GnRH for the COH cycle has resulted in reasonable IVF outcomes in infertile women (8)(9). Therefore, we used half doses of the depot form of GnRH agonist to suppress the ovary.…”

“…Forty-nine patients underwent the GnRH-antagonist protocol. Corifollitropin alfa was administered on the menstrual cycle day 3. programs before their integration into daily use and have resulted in reasonable outcomes (6)(7)(8)(9). Furthermore, the drug industry may force the use of these innovative options, making them more popular.…”