Your San Diego fertility center: Reproductive Sciences Center & Genetics Institute

Early administration of additional vaginal progesterone support has a detrimental effect on implantation rates in embryo recipient cycles.

Objective: Increasing evidence suggests that micronized intravaginal progesterone (IV-P) is as effective as intramuscular (IM-P) in providing luteal support in embryo recipient cycles; however, the optimal dosage of IV-P has not been established. The aim of this study was to examine the effect of
an increased dose of IV-P early in the luteal phase.

Design: Retrospective data analysis from embryo recipient cycles over a two-year period in a private
clinic.

Materials and Methods: Down-regulated patients were treated with biweekly IM estradiol valerate
and P was initiated on cycle day 12 in frozen embryo transfer cycles or on the day of egg retrieval in
egg donation cycles. Patients received one of three P regimens: 200 mg IV-P BID (n=95), 400 mg IVP
BID (n=46) or 50 mg/day IM-P in oil (n=29). On the day of ET, the P dose in each regimen was
doubled. Serum P levels were measured on the day of ET and 1 week later. Cycle outcomes were
compared for each of the 3 regimens.

Results: Mean recipient age (34.7 7y) and number of embryos transferred (2.7 0.9) were comparable
for the 3 regimens. Serum P levels with 200 mg IV-P were significantly lower compared to IM-P,
both on the day of ET and one week later (17.8 vs. 22 and 30.5 vs. 43.6 ng/ml respectively, p<0.05),
as were serum P levels with 400 mg IV-P compared to IM-P one week after ET (29.8 vs. 43.6 ng/ml;
p<0.05). There was no significant difference between serum P levels with 200 and 400 mg IV-P.
Pregnancy and implantation rates were significantly lower in recipients using 400 mg compared to 200
mg capsules when transfers were performed on day 2 or 3 of P support (54% and 25% for 400 mg, vs.
75% and 42% for 200 mg respectively; p<0.05) but not when extended culture was used. Within the
400 mg IV-P group, pregnancy (54% vs. 75%, p<0.05) and implantation rates (25% vs.47%, p<0.05)
were significantly higher when the increase in P dose occurred on day 4-5 rather than day 2-3 of luteal
support. There were no significant differences in outcomes between the 200 mg IV-P and IM-P
regimens or in miscarriage rates among the 3 regimens.

Conclusions: Increased doses of IV-P initiated during early (days 2 or 3), but not late (days 4 or 5), P
luteal support are associated with reduced pregnancy and implantation rates in recipient cycles. This
study suggests that high doses of vaginal P administered early in the luteal phase may have a
detrimental effect on implantation, possibly due to accelerated endometrial maturation resulting in an
alteration of the window of implantation.

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