Comparison between different routes of progesterone administration as luteal phase support in infertility treatments.

Centre for Reproductive Mediciney, Dutch-Speaking Free University of Brussels, Belgium.
Human Reproduction Update (Impact Factor: 8.66). 03/2000; 6(2):139-48.
Source: PubMed

ABSTRACT Different routes of natural progesterone supplementation have been tried as luteal phase support in infertility treatments. Orally administered progesterone is rapidly metabolized in the gastrointestinal tract and its use has proved to be inferior to i.m. and vaginal routes. Progesterone i.m. achieves serum progesterone values that are within the range of luteal phase and results in sufficient secretory transformation of the endometrium and satisfactory pregnancy rates. The comparison between i.m. and vaginal progesterone has led to controversial results as regards the superiority of one or the other in inducing secretory endometrial transformation. However, there is increasing evidence in the literature to favour the use of vaginal progesterone. Vaginally administered progesterone achieves adequate endometrial secretory transformation but its pharmacokinetic properties are greatly dependent on the formulation used. After vaginal progesterone application, discrepancies have been detected between serum progesterone values and histological endometrial features. Vaginally administered progesterone results in adequate secretory endometrial transformation, despite serum progesterone values lower than those observed after i.m. administration, even if they are lower than those observed during the luteal phase of the natural cycle. This discrepancy is indicative of the first uterine pass effect and therefore of a better bioavailability of progesterone in the uterus, with minimal systematic undesirable effects.

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    ABSTRACT: Context: Progesterone vaginal insert (PVI), an effervescent delivery system dissolves rapidly, is absorbed through the vaginal epithelium, and achieves higher endometrial tissue concentrations than those achieved with progesterone in oil (PIO) given intramuscularly (IM). Objective: To examine the pharmacokinetics (PK) and pharmacodynamics (PD) of PVI compared to PIO. Design, Setting and Participants: Fifty-eight healthy premenopausal women were randomized to PVI 50 mg, 100 mg, or 200 mg once-daily, or 100 mg or 200 mg twice-daily, or PIO 50-mg IM injection once-daily for 10 days. Serum samples were obtained after the first dose; serum and endometrial tissue were obtained after the last dose. Main Outcome Measures: Maximum observed serum concentration (Cmax), time to Cmax (Tmax), area under the serum-concentration time curve over the dosing interval (AUC) were calculated after correcting for baseline progesterone concentrations. Analysis of Variance and paired t test were used to compare results across and within groups. Results: Higher Cmax was observed after PIO than PVI administration. Endometrial tissue progesterone concentrations were higher for PVI regimens. Tmax was 7.3 hours after PIO and 3.3 to 5.9 hours after PVI. Steady state was achieved within 24 and 48 hours for PVI and PIO regimens, respectively. AUC increased with increasing PVI dosage; however, the increase was not proportional to the increase in dosage. Downregulation of estrogen and progesterone receptors was observed in secretory biopsy specimens. Conclusion: The PVI system consistently allowed for rapid progesterone absorption; achieved higher endometrial tissue concentrations and lower systemic exposures than observed after PIO IM.
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    ABSTRACT: To summarize the available published randomized controlled trial data regarding timing of P supplementation during the luteal phase of patients undergoing assisted reproductive technology (ART). A systematic review. Not applicable. Undergoing IVF. Different starting times of P for luteal support. Clinical pregnancy (PR) and live birth rates. Five randomized controlled trials were identified that met inclusion criteria with a total of 872 patients. A planned meta-analysis was not performed because of a high degree of clinical heterogeneity with regard to the timing, dose, and route of P. Two studies compared P initiated before oocyte retrieval versus the day of oocyte retrieval and PRs were 5%-12% higher when starting P on the day of oocyte retrieval. One study compared starting P on day 6 after retrieval versus day 3, reporting a 16% decrease in pregnancy in the day 6 group. Trials comparing P start times on the day of oocyte retrieval versus 2 or 3 days after retrieval showed no significant differences in pregnancy. There appears to be a window for P start time between the evening of oocyte retrieval and day 3 after oocyte retrieval. Although some studies have suggested a potential benefit in delaying vaginal P start time to 2 days after oocyte retrieval, this review could not find randomized controlled trials to adequately assess this. Further randomized clinical trials are needed to better define P start time for luteal support after ART. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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    ABSTRACT: To assess the efficacy of luteal phase support (LPS) using intravaginal progesterone (P) on pregnancy rate in Iranian women with polycystic ovarian syndrome (PCOS) who used a combination for ovulation induction consisting of letrozole or clomi- phene citrate (CC) and human menopausal gonadotropin (HMG).

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