The hormonal flare-up following gonadotrophin-releasing hormone agonist administration is influenced by a progestogen pretreatment

Abstract

In a short-term protocol, the influence of progestogen pretreatment upon the oestradiol flare-up (delta E2) induced by gonadotrophin-releasing hormone agonist (GnRHa) was assessed in relation to in-vitro fertilization (IVF) outcome in 90 cycles programmed (n = 52) or not (n = 38) by norethisterone (10 mg/day for 12-20 days). Patients pretreated by progestogen had a significantly lower delta E2 value than patients without pretreatment (delta E2 = 26 +/- 5 versus 61 +/- 8 pg/ml, P = 0.003). It could be related to a lower gonadotrophic response for luteinizing hormone (LH) (delta LH = 9 +/- 0.8 versus 14.5 +/- 2.2 IU/l, P = 0.01). The IVF outcome (final oestradiol, number of oocytes or embryos) was similar in both groups and delta E2 was well correlated with these final parameters in each group. A significant rise in serum progesterone was observed only in patients without pretreatment (delta P = 1.1 +/- 0.2 versus 0.1 +/- 0.1 ng/ml, P < 0.0001). Thus norethisterone pretreatment decreases the oestradiol flare-up and prevents the early increase of progesterone (by avoiding some rescue of the corpus luteum or some luteinization of small developing follicles) but does not influence the outcome of the IVF cycle. In clinical practice, evaluation of the hormonal flare-up for predicting IVF outcome must take into account any pretreatment prescription.

Management of poor responders: can outcomes be improved with a novel gonadotropin-releasing hormone antagonist/letrozole protocol?

“…The use of this agent may have reduced the potential for corpus luteum rescue with ML but not during letrozole and gonadotropin administration during the early follicular phase (32,33). A recent study has shown that a luteal-phase E 2 patch may improve response in antagonist cycles also by potentially eliminating a preexisting corpus luteum (34).…”

Oral contraceptive pretreatment does not improve outcome in microdose gonadotrophin-releasing hormone agonist protocol among poor responder intracytoplasmic sperm injection patients

“…Microdose GnRH-a flare regimens were designed to take advantage of the release of endogenous gonadotrophins induced by administration of GnRH-a in the early folicular phase while inhibiting subsequent LH surges [12,14]. Hypothalamicpituitary suppression in IVF patients may also be achieved with the use of OCs or progestins alone [13,15]. Among the treatments proposed to improve the ovarian response in poor responders, OC pretreatment is considered as a possible option [14].…”

Aromatase inhibitors prevent the estrogen rise associated with the flare effect of gonadotropins in patients treated with GnRH agonists

“…A significant decrease in the number of functional ovarian cysts 1 week after GnRH-a therapy, indicative of rapid pituitary inhibition, was observed with both progestin and OC use (20,21). In addition, Cedrin-Durnerin et al (22) showed that progestin pretreatment was able to reduce the peak estrogen concentrations after GnRH-a compared with patients not assigned to the pretreatment. The postulated mechanism was to minimize the response of the pituitary gonadotropin secretion in response to GnRH-a.…”