Major Finding: Among nonpregnant women, the incidence of luteal phase bleeding was significantly higher at 56.5% in women treated with Crinone vs. 38% in those given intramuscular progesterone.
Data Source: A prospective trial involving 365 patients.
Disclosures: The study was supported in part by EMD Serono Inc., which distributes Crinone. Dr. Yanushpolsky disclosed receiving compensation from Columbia Laboratories for time and travel expenses to present the data. Her coauthors disclosed being members of the scientific advisory boards for MediCult, Humagen, MidAtlantic Diagnostics, WIN Fertility, and EMD Serono.
ATLANTA — Intramuscular progesterone delayed the onset of luteal phase bleeding, compared with Crinone 8% progesterone vaginal gel in nonpregnant women undergoing in vitro fertilization and embryo transfer in a prospective trial involving 365 patients.
“This isn't necessarily a good thing because it gives them false hope,” lead researcher Dr. Elena Yanushpolsky said in an interview. “Patients think they're pregnant for a longer time when they're not, and the injections are painful.”
Several meta-analyses as well as a recent large prospective, randomized trial have compared the efficacy of Crinone and intramuscular progesterone (IMP) for luteal phase support during in vitro fertilization (IVF) and reported similar pregnancy rates and IVF cycle outcomes.
However, a few studies observed an increased incidence of luteal phase bleeding in patients supplemented with Crinone.
In the current study, patient-reported luteal phase bleeding occurred with equal frequency among pregnant patients in the Crinone and IMP arms (22% vs. 19%). This was true for ongoing pregnancies (13% vs. 18%), as well as for failed pregnancies (40.5% vs. 21%).
Among nonpregnant women, however, the incidence of luteal phase bleeding was significantly higher at 56.5% in women treated with Crinone vs. 38% in those given IMP.
This effect was ameliorated by the administration of estrogen, according to Dr. Yanushpolsky and her colleagues at the Brigham and Women's Hospital in Boston.
“It's an issue of hormone metabolism, but not efficacy,” she said.
Overall, pregnancy rates were similar at 67% among the 190 Crinone patients vs. 64% among the 175 IMP patients, the investigators reported in a poster at the annual meeting of the American Society for Reproductive Medicine.
There were no differences in age or day 3 follicle-stimulating hormone (FSH) levels between patients who experienced bleeding and those who did not, but those who had luteal phase bleeding had significantly lower pregnancy and delivery rates, and a significantly higher likelihood of failed pregnancy.
The investigators theorized that IMP may delay bleeding because of some metabolite, while the addition of estrogen may play a role in delaying the breakdown of the endometrial lining in nonpregnant women given Crinone.
Dr. Yanushpolsky noted that anecdotally, clinicians were also reporting a low incidence of luteal phase bleeding with estrogen supplementation in women receiving either IMP or Crinone.
This prompted a post hoc analysis in 90 patients who received luteal estrogen supplementation in addition to their study medication, demonstrating that estrogen supplementation reduces luteal phase bleeding, but does not improve IVF outcomes.
Overall, patients supplemented with estrogen experienced significantly fewer episodes of luteal phase bleeding than those who did not receive estrogen (14% vs. 35%, P = .0002).
This was true within the Crinone (17% vs. 38%) and IMP treatment arms (12% vs. 30%), and among nonpregnant (23% vs. 55%) and pregnant (10% vs. 24%) patients.
Pregnancy rates, however, were similar at 64% among those who received estrogen support vs. 65% among those who did not.
Likewise, there was no difference in pregnancy rates when patients received estrogen supplementation or did not in either the Crinone arm (65% vs. 67%) or IMP arm (63% vs. 62%).
Women in the study received either IMP 50 mg/day starting 24 hours after egg retrieval or Crinone 8% gel starting 48 hours after retrieval. Their mean age was 34 years.