To evaluate the efficacy of oral micronized progesterone compared with IM progesterone in oil for luteal support in patients undergoing IVF who are treated with a GnRH agonist.
Design
Randomized prospective clinical trial.
Setting
University-based IVF center.
PATIENT(S): Women <40 years of age who were undergoing IVF with luteal GnRH pituitary down-regulation.
INTERVENTION(S): Patients were randomized to receive either oral micronized progesterone (200 mg three times daily) or IM progesterone (50 mg daily).
MAIN OUTCOME MEASURE(S): Progesterone levels at standardized days 21 and 28, and pregnancy and embryo implantation rates.
RESULT(S): Day 21 progesterone levels were 77.6+/-13.2 ng/mL in the IM group and 81.5+/-16.2 ng/mL in the oral group. Day 28 progesterone levels were 76.3+/-15.0 ng/mL in the IM group and 53.6+/-10.1 ng/mL in the oral group. The clinical pregnancy rates were 57.9% and 45.8% for the IM and oral groups, respectively. The implantation rate per embryo was significantly higher in the IM group (40.9%) than in the oral group (18.1%).
CONCLUSION(S): When used according to our protocols, oral progesterone and IM progesterone result in comparable levels of circulating progesterone. However, oral progesterone results in a reduced implantation rate per embryo.
PMID 10202868 10202868 DOI 10.1016/s0015-0282(98)00515-9 10.1016/s0015-0282(98)00515-9
Cite this article
Licciardi, F. L., Kwiatkowski, A., Noyes, N. L., Berkeley, A. S., Krey, L. L., & Grifo, J. A. (1999). Oral versus intramuscular progesterone for in vitro fertilization: a prospective randomized study. Fertility and sterility, 71(4), 614-618. https://doi.org/10.1016/s0015-0282(98)00515-9
Licciardi FL, Kwiatkowski A, Noyes NL, Berkeley AS, Krey LL, Grifo JA. Oral versus intramuscular progesterone for in vitro fertilization: a prospective randomized study. Fertil Steril. 1999;71(4):614-618. doi:10.1016/s0015-0282(98)00515-9
Licciardi, F. L., et al. "Oral versus intramuscular progesterone for in vitro fertilization: a prospective randomized study." Fertility and sterility, vol. 71, no. 4, 1999, pp. 614-618.
To compare the efficacy of Crinone 8% intravaginal progesterone gel vs. IM progesterone for luteal phase and early pregnancy support after IVF-ET. Randomized, open-label study. Academic medical center. PATIENT(S): Two hundred and one women undergoing IVF-ET. INTERVENTION(S): Women were randomized to supplementation with Crinone 8% (90 mg once daily) or IM progesterone (50 mg once daily) beginning the day after oocyte retrieval. MAIN OUTCOME MEASURE(S): Pregnancy, embryo implantation, and live birth rates. RESULT(S): The women randomized to luteal phase supplementation with IM progesterone had significantly higher clinical pregnancy (48.5% vs. 30.4%; odds ratio [OR], 2.16; 95% confidence interval [CI], 1.21, 3.87), embryo implantation (24.1% vs. 17.5%; OR, 1.89; 95% CI, 1.08, 3.30), and live birth rates (39.4% vs. 24.5%; OR, 2.00; 95% CI, 1.10, 3.70) than women randomized to Crinone 8%. CONCLUSION(S): In women undergoing IVF-ET, once-a-day progesterone supplementation with Crinone 8%, beginning the day after oocyte retrieval, resulted in significantly lower embryo implantation, clinical pregnancy, and live birth rates compared with women supplemented with IM progesterone.
InfertilityEmbryo Transfer OptimizationUterine ContractilityLuteal Phase Support
To investigate whether uterine contractility at the time of embryo transfer (ET) can be reduced by early onset of luteal support with progesterone administered vaginally. Prospective analysis. Assisted reproduction unit. PATIENT(S): Eighty-four women undergoing 84 GnRH-a and FSH/hCG cycles for IVF-ET were studied. INTERVENTION(S): Vaginal progesterone was randomly started on the day of oocyte retrieval (group A, n = 43) or on the evening of ET (group B, n = 41). On the day of hCG administration and just before ET, 2-minute sagittal uterine scans were obtained by ultrasound and digitized with an image analysis system for assessing uterine contraction frequency. MAIN OUTCOME MEASURE(S): Uterine contraction frequency. RESULT(S): Whereas uterine contraction frequency was similar in both groups on the day of hCG (4.6 +/- 0.3 and 4.5 +/- 0.3 contractions per minute, respectively), only women in group A showed decreased uterine contraction frequency on the day of ET (2.8 +/- 0.2 vs. 4.2 +/- 0.3 contractions per minute). CONCLUSION(S): Vaginal progesterone administration starting on the day of oocyte retrieval induced a decrease in uterine contraction frequency on the day of ET as compared with preovulatory values. Uterine relaxation before ET is likely to improve IVF-ET outcome by avoiding the displacement of embryos from the uterine cavity.
To determine whether the use of luteal phase support improves pregnancy rate (PR) in infertility. A meta-analysis of randomized trials of luteal phase support. Search of the National Library of Medicine MEDLINE data base from 1971 using the words luteal, pregnancy, human, and comparative. Bibliography of relevant articles, reviews, and abstracts of scientific meetings were hand searched. All randomized controlled trials of luteal phase support in infertility were included. Luteal phase support for recurrent abortion and nonrandomized trials were excluded. The common odds ratio was calculated for each intervention using the Mantel-Haentzel test. Homogeneity of treatment effect was evaluated using the Breslow-Day test. Pregnancy per cycle, rate of spontaneous abortion, and ovarian hyperstimulation syndrome rate. Eighteen trials met the above criteria. Human chorionic gonadotropin improved PRs in IVF when GnRH agonist (GnRH-a) was used (n = 151) and was superior to P (n = 352). Its benefit in all IVF cycles, however, was not established because of significant heterogeneity of treatment effect. Progesterone improved the PR in all IVF cycles (n = 457). No significant reduction in spontaneous abortion was noted with luteal support (n = 200). Ovarian hyperstimulation syndrome occurred in 5% of patients with hCG. Combination of data from trials of luteal support with other infertility therapies was not possible because of the differences in patient populations. The meta-analysis supports the routine use of hCG in IVF cycles using a GnRH-a. Progesterone was also beneficial for luteal phase support in IVF. For other infertility therapy, however, further research is needed to evaluate the role of luteal phase support.
Reproductive EndocrinologyPharmacokineticsRoute of AdministrationProgesterone Formulations
To examine the effects of food ingestion and administered dose on the absorption of oral micronized P (Utrogestan; Besins-Iscovesco, Paris, France) and to compare the bioavailability of intramuscular versus oral routes of administration. Prospective, randomized, open label crossover protocol with 7 days between dosages. Academic institution. Fifteen normal postmenopausal women. All subjects participated [1] micronized P (200 mg) or placebo under fasting or nonfasting conditions once daily for 5 days; [2] micronized P (100, 200, or 300 mg) once daily under fasting conditions for 5 days; and [3] micronized P (200 mg) or intramuscular P (50 mg in oil) administered once daily for 2 days. Serum P concentrations were measured in all groups. Concomitant food ingestion increased the area under the serum P concentration versus time curve (AUC0 to 24) and the maximum serum P concentration (Cmax) without affecting time to maximum serum concentration (Tmax) (P < 0.05). Micronized P absorption and elimination were first-order processes and exhibited dose-independent pharmacokinetics between 100 and 300 mg. After intramuscular P, Cmax was higher and Tmax occurred later compared with the oral P preparation. Oral P had lower relative bioavailability (8.6%) than intramuscular P. Absorption of micronized P was enhanced twofold in the presence of food. Both absorption and elimination were dose-independent, dose proportionality being confirmed. Bioavailability of the oral P was approximately 10% compared with intramuscular P.