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: 10.17). 03/2000; 6(2):139-48.
Source: PubMed


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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Available from: Paul Devroey, Sep 23, 2014
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    • "However, there has been a viewpoint projected that measuring serum progesterone for adequacy of pessary dosage and effect is irrelevant, as pessaries placed in the vagina somehow act directly on the endometrium , initially described as the first uterine pass effect (Bulletti et al., 1997), where radioactive (tritiated) progesterone was shown to travel from vagina to uterus in cadaveric specimens. Consequently, several clinical groups view vaginal administration of progesterone as superior to other routes (Ho et al., 2008; Manno et al., 2005; Tavaniotou et al., 2000). Conversely, a recent investigation has demonstrated that vaginal gel and intramuscular injection of progesterone showed comparable implantation and pregnancy rates in IVF patients receiving vitrified blastocysts (Shapiro et al., 2014). "
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    ABSTRACT: This study explores the relevance of mid-luteal serum hormonal concentrations in cryopreserved embryo transfer cycles conducted under hormone replacement therapy (HRT) control and which involved single-embryo transfer (SET) of 529 vitrified blastocysts. Widely ranging mid-luteal oestradiol and progesterone concentrations ensued from the unique HRT regimen. Oestradiol had no influence on clinical pregnancy or live birth rates, but an optimal progesterone range between 70 and 99 nmol/l (P < 0.005) was identified in this study. Concentrations of progesterone below 50 nmol/l and above 99 nmol/l were associated with decreased implantation rates. There was no clear interaction between oestradiol and progesterone concentrations but embryo quality grading did show a significant influence on outcomes (P < 0.001 and P = 0.002 for clinical pregnancy and live birth rates, respectively). Multiple comparison analysis showed that the progesterone effect was influential regardless of embryo grading, body mass index or the woman's age, either at vitrification or at cryopreserved embryo transfer. The results support the argument that careful monitoring of serum progesterone concentrations in HRT-cryopreserved embryo transfer is warranted and that further studies should explore pessary adjustments to optimize concentrations for individual women to enhance implantation rates. Copyright © 2015 Reproductive Healthcare Ltd. All rights reserved.
    Full-text · Article · May 2015 · Reproductive biomedicine online
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    • "For the vaginal administration of natural micronized progesterone , no dose finding studies have been performed. Most frequently , 300 – 600 mg of natural micronized progesterone is administered daily, spread over two to three dosages (Tavaniotou et al., 2000). However, further prospective randomized trials are essential to define the necessary dose of vaginal micronized progesterone for LPS in IVF. "
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    ABSTRACT: Stimulated IVF cycles are associated with luteal phase defect. In order to overcome this, different doses, durations and types of luteal phase support (LPS) have been evaluated. There is still no agreement regarding the optimal supplementation scheme. The aim of this paper is to assess the past and the current clinical practices of luteal supplementation in IVF. The databases of Medline and PubMed were searched to identify relevant publications. LPS with human chorionic gonadotrophin (hCG) [n = 262, odds ratio (OR) 2.72 (95%), confidence interval (CI) 1.56–4.90, P < 0.05] or progesterone (n = 260, OR 1.57 CI 1.13, 2.17, P < 0.05) results in an increased pregnancy rate compared with placebo, however, hCG is associated with increased risk of ovarian hyperstimulation syndrome. Natural micronized progesterone is not efficient if taken orally. The data on oral dydrogesterone are still conflicting. Vaginal and intra muscular progesterone have comparable outcomes. The addition of estradiol (E2) seems to be beneficial in long GnRH agonist protocol (implantation rate 39.6% with E2 compared with no E2; P < 0.05) but not in the short GnRH agonist and GnRH antagonist protocol. Despite the early promising results, it is too early to recommend the use of GnRH agonist in LPS. LPS should cease on the day of positive HCG. Since the cause of luteal phase defect in IVF appears to be related to the supraphysiological levels of steroids, milder stimulation protocols should be advocated in order to eventually overcome the luteal phase defect.
    Full-text · Article · Sep 2007 · Human Reproduction Update
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    • "I.m. injections of progesterone can be painful and may lead to marked inflammation and even to sterile abscess formation at the injection site (Tavaniotou et al., 2000). Vaginal application of progesterone has been reported to cause local irritation and vaginal discharge (Kimzey et al., 1991). "
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    ABSTRACT: We report two cases of acute eosinophilic pneumonia induced by i.m. administration of progesterone used as luteal phase support after IVF. For both patients, the symptoms began 3 weeks after the first injection of progesterone. Both patients were in respiratory distress, and one of them required ventilatory assistance for a week, with 5 days in the intensive care unit. Symptoms improved as the i.m. form was shifted to a vaginal form of progesterone together with the administration of corticosteroids. Sesame oil (used as excipient) and benzyl alcohol (used as preservative) could both be incriminated in the development of the hypersensitivity reaction. The need for luteal phase support is clearly established in IVF cycles with GnRH agonist protocols, and progesterone is the generally recommended compound. However, there is no definitive consensus regarding the optimal route of administration of progesterone. These two cases of acute drug-induced disease show that the use of i.m. progesterone can be associated with a severe morbidity in otherwise healthy young patients. This is an additional argument to advocate the use of vaginal progesterone as luteal support in IVF.
    Full-text · Article · Sep 2004 · Human Reproduction
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