Timing of Initiation of Luteal Phase Support in Poor Responders Undergoing IVF/ICSI: a Randomized Controlled Trial

The optimal stimulation protocol for poor responder patients is a therapeutic challenge. However the lack of initial central down-regulation in early follicular phase and adequate prevention of premature luteinizing hormone (LH) surge in late follicular phase provide GnRH antagonist protocol as a potentially proper option for poor responders . Significant reduction in gonadotropin dosage and stimulation period could be achieved by antagonist protocol. Nevertheless, there are no significant differences in terms of clinical pregnancy and cancellation rates between the GnRH antagonist and agonist in poor responder patients .

a study evaluated the nonsupplemented luteal phase characteristics in patients undergoing ovarian stimulation with recombinant FSH and GnRH-antagonist cotreatment. With the administration of GnRH antagonist, luteolysis started prematurely because of excessive negative steroid feedback, resulting in suppressed pituitary LH release; low pregnancy rates were observed . In another study, the endometrium demonstrated abnormal development in oocyte donors who were stimulated with a GnRH-antagonist protocol but not supplemented in the luteal phase . Low luteal LH serum concentration and shortened luteal phase indicated the need for luteal phase supplementation in GnRH-antagonist IVF cycles .

Luteal phase support with hCG or progesterone after assisted reproduction results in an increased pregnancy rates . Natural micronized progesterone is not efficient if taken orally . The oral dydrogesterone (DG) might be sufficient for luteal supplementation in IVF cycles, however more large randomized controlled trials are needed before a conclusion about oral DG can be drawn . Vaginal and IM progesterone seem to have comparable implantation and clinical pregnancy rates and delivery rates . Concomitant use of E2 with progesterone after stimulation with rec-FSH and GnRH antagonist does not enhance the probability of pregnancy . Although there have been attempts to introduce GnRH agonist as a novel LPS in stimulated IVF cycles to improve PR, it is too early to adopt this approach across the board .

Timing of LPS remains the subject of debate, current clinical practice involves beginning LPS on different days. Starting progesterone on the day before oocyte retrieval or waiting until day 6 after retrieval may result in lower pregnancy rates. There appears to be a window for progesterone start time between the evening after oocyte retrieval and day 3 after oocyte retrieval. Although some have suggested a potential benefit in delaying vaginal progesterone starting time to 2 days after oocyte retrieval. It remains unclear whether pregnancy rates can be improved by delaying the progesterone initiation until the end of this progesterone window to avoid endometrial advancement . Additional randomized clinical trials are needed to better define progesterone start time for luteal support, particularly for vaginal progesterone, which may more rapidly advance the endometrium .

2. OBJECTIVES Research hypothesis: in poor responder women undergoing IVF/ICSI, starting luteal phase support (LPS) on day of ovum retrieval or 2 days later may have similar pregnancy rates.