Oral versus intramuscular progesterone for in vitro fertilization: a prospective randomized study

Frederick L Licciardi; Andrea Kwiatkowski; Nicole L Noyes; Alan S Berkeley; Lewis L Krey; Jamie A Grifo

doi:10.1016/s0015-0282(98)00515-9

Pregnancy · Preconception Care

Oral versus intramuscular progesterone for in vitro fertilization: a prospective randomized study

Licciardi FL, Kwiatkowski A, Noyes NL, Berkeley AS, Krey LL, Grifo JA

Published April 15, 1999 Fertility and Sterility, 71(4), 614-618

DOI 10.1016/s0015-0282(98)00515-9 PMID 10202868

RRM Academy Synopsis

Oral progesterone gave lower embryo implantation than injection in IVF

In a randomized trial during IVF, oral progesterone gave a lower embryo implantation rate than injections. The trial assigned 19 women to injections and 24 to oral progesterone. About 18 out of 100 embryos implanted with oral progesterone, against 41 out of 100 with injections. Clinical pregnancy rates did not differ significantly.

Key Findings

The implantation rate per embryo was 40.9% with intramuscular progesterone and 18.1% with oral progesterone (P = .004), a greater than twofold lower rate in the oral group.
Clinical pregnancies occurred in 11 of 19 women (57.9%) given injections and 11 of 24 women (45.8%) given oral progesterone. The authors report no significant difference.
Blood progesterone levels on days 21 and 28 did not differ significantly between the groups, including among women who were not pregnant. The lowest individual levels occurred in the oral group.
Multiple implantation occurred in 9 of 11 pregnant women in the injection group and 4 of 11 in the oral group. All four higher-order multiple implantations were in the injection group.
Two miscarriages occurred in the oral group, one of them chromosomally abnormal, and none in the injection group.

Interpretation

The study is a randomized trial at one university IVF center. Women were recruited through waiting-room signs and assigned by a randomization table. The authors ended enrollment early for ethical reasons and state that the small groups lowered the power to detect differences in pregnancy rates or progesterone levels. Findings cover women under 40 using a GnRH agonist and the oral formulation and schedule tested. The authors write that they can only guess at why implantation was lower. The report gives no live birth outcome.

RRM Context

The authors explain that the GnRH agonist suppresses pituitary hormone release for up to 12 days after it is stopped and shortens the luteal phase. Progesterone is then given from outside. The trial compares two routes for that replacement. Restorative reproductive medicine evaluates ovulation and the luteal phase in a woman's own cycle.

Our editorial summary of this paper, not the article's abstract.

Abstract

Objective

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.

Patients

Women <40 years of age who were undergoing IVF with luteal GnRH pituitary down-regulation.

Interventions

Patients were randomized to receive either oral micronized progesterone (200 mg three times daily) or IM progesterone (50 mg daily).

Main Outcome Measures

Progesterone levels at standardized days 21 and 28, and pregnancy and embryo implantation rates.

Results

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%).

Conclusions

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.

Topics

Pregnancy › Preconception Care › Preconception Optimization · Reproductive Endocrinology › Luteal Phase › Progesterone Support · Therapeutics › Hormonal Agents › Progesterone and Progestins

Frederick L Licciardi, Andrea Kwiatkowski, Nicole L Noyes, Alan S Berkeley, Lewis L Krey, Jamie A Grifo

Fred Licciardi, F Licciardi, A Kwiatkowski, N Noyes, A Berkeley, L Krey, J Grifo

PMID 10202868 10202868 DOI 10.1016/s0015-0282(98)00515-9 10.1016/s0015-0282(98)00515-9 Licciardi et al. 1999, Licciardi 1999

Keywords

Administration, Oral, Adult, Embryo Implantation, Embryo Transfer, Female, Fertilization in Vitro, Humans, Injections, Intramuscular, Pregnancy, Pregnancy Outcome, Progesterone/administration & Dosage/blood, Prospective Studies, Progesterone

Oral versus intramuscular progesterone for in vitro fertilization: a prospective randomized study

Oral progesterone gave lower embryo implantation than injection in IVF

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

Using outcome data from one thousand mosaic embryo transfers to formulate an embryo ranking system for clinical use

The incidence of luteal phase defect in normal, fertile women, determined by serial endometrial biopsies

Related research

A randomized study comparing Crinone 8% and intramuscular progesterone supplementation in in vitro fertilization-embryo transfer cycles

Luteal support after in-vitro fertilization: Crinone 8%, a sustained release vaginal progesterone gel, versus Utrogestan, an oral micronized progesterone

A prospective randomized study comparing intramuscular progesterone and 17alpha-hydroxyprogesterone caproate in patients undergoing in vitro fertilization-embryo transfer cycles

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

Keywords