IVF Protocol for Poor Responders

"Stop Lupron Protocol"

This is an excerpt from an article in the online Oxford Medical Journals I read recently.  This is only a portion - there is more good information about poor response and ICSI, poor response and the likelyhood of ovarian failure, etc.
A rational approach to the management of low responders in in-vitro fertilization: Opinion

We prospectively evaluated the `stop-Lupron' protocol (Faber et al., 1998) at our Center (Karande et al., 1997b) Improved pregnancy rate in poor responder patients with cessation of GnRHa down-regulation prior to stimulation with high dosages of gonadotrophins. The study population included 82 consecutive low responders who underwent IVF–embryo transfer between January 1996 and October 1996. Low responders were defined as patients with either a history of a cancelled cycle or low response with standard protocol [peak oestradiol <500 pg/ml (1835.5 pmol/l), or <= 4 mature oocytes retrieved (n = 56)]. However, we also included patients with suspected abnormal ovarian reserve because we prospectively anticipated a low response in such patients. These included patients with an elevated day 3 FSH [>7 but <12 mIU/ml (7 pmol/l), n = 33] and/or elevated day 3 oestradiol concentration [>75 pg/ml (275.3 pmol/l), n = 8] in a non-treatment cycle (Smotrich et al., 1995) and patients' age >= 40 years (n = 24). Some patients had more than one abnormality. Patients with a day 3 FSH >12 mIU/ml [equivalent to a concentration of 25 mIU/ml using the Leeco assay (Scott et al., 1991)] were excluded from the study as, historically, we have not had a single live-birth in this group of patients. Twenty-six cycles (31.6%) were cancelled due to poor ovarian response. Fifty-one low responders reached retrieval and 48 had an embryo transfer. None of the patients had a premature LH surge. Based on a presumed low oocyte quality we were liberal with the number of embryos transferred in the low responder group (4.1 ± 2) and none therefore had any excess embryos for cryopreservation. The clinical pregnancy rate per started cycle was 19.5% (16/82) and per retrieval 31.4% (16/51). Surprisingly, we had a very high incidence of multiple pregnancies (43.8%). Of the 16 pregnancies, seven were singleton, five were twin, two were triplet, and there were two quadruplet pregnancies. This is in contrast to a similar group of patients, which were stimulated with a `flare' protocol where we had a dismal success rate (Karande et al., 1997a). Increasing the number of embryos transferred in low responder patients, therefore, does not seem to be a good strategy. We are currently investigating the role of blastocyst transfer in low responder patients (Gardner et al., 1998).

The mechanism by which the `stop-Lupron' protocol apparently improves ovarian responsiveness is unknown. It is possible that Lupron has a direct inhibitory effect on the ovaries and that, by reducing the dose or stopping it altogether, it removes this suppression and increases ovarian response (Parinaud et al., 1992; Kowalik et al., 1998). The mechanism of continued suppression (despite 11.1 ± 1.5 days of stimulation) of premature LH surges under this protocol is presently also still unknown and needs to be further investigated. Continuous suppression of LH after stopping leuprolide acetate has been reported (Sungurtekin and Jansen, 1995): a brief, 5 day course of GnRHa appeared to suppress endogenous GnRH activity for at least 1 week afterwards. In 19 patients, after stopping leuprolide acetate, LH was often undetectable within 48 h and remained so for at least 7 days.