Progesterone vaginal ring versus vaginal gel for luteal support with in vitro fertilization A randomized comparative study

Luteal supplementation with a weekly progesterone vaginal ring or daily vaginal gel provided similar high clinical pregnancy rates in in vitro fertilization.

Laurel Stadtmauer, M.D., Ph.D., Kaylen M. Silverberg, M.D., Elizabeth S. Ginsburg, M.D.

Volume 99, Issue 6, Pages 1543-1549, May 2013


To compare the efficacy and safety of luteal phase support in IVF with a progesterone (P) vaginal ring or gel (VR or VG).

Prospective, randomized, single-blind, multicenter, phase III clinical trial ( identifier: NCT00615251).

Nineteen private and 3 academic high-volume US IVF centers.

1,297 infertile patients were randomized to a weekly progesterone vaginal ring (VR, n=646) or a daily progesterone 8% vaginal gel (VG, n=651).

IVF was performed per site-specific protocols. The day after egg retrieval (ER), patients were randomized and began VR or VG therapy, which continued for up to 10 weeks’ gestation.

Main Outcome Measures:
Clinical pregnancy rates at 8 and 12 weeks of pregnancy; rates of biochemical pregnancy, live birth, spontaneous abortion, ectopic pregnancy, and cycle cancellation; and safety and tolerability were secondary measures.

Clinical pregnancy rates at 8 and 12 weeks were high and comparable between groups: 48.0% for VR and 47.2% for VG at week 8 and 46.4% (VR) and 45.2% (VG) at week 12. Live birth rates were 45% (VR) and 43% (VG). Adverse event (AE) profiles were similar between groups.

The weekly progesterone VR provided similar pregnancy rates to the daily VG, with no major differences in safety.

  • fertilitydoc

    I want to commend the authors for this excellent paper– but which
    raises some new important questions. Is the ring to be thought of as
    just a novel delivery system or is there more to this? I am interested
    din the authors explanations as to why 1) the timing of the start of the
    vag prog ring here is different than in Dr Silverberg’s other paper on
    vag prog (then 2 days post retrieval and here 1 day earlier) and 2) Why
    the results are so different than in Dr Ginsberg’s previous studies on
    vaginal prog whch showed much worse results than IM prog (discussed in
    the excellent online journal club online)– but again the day on onset
    was different again. What do the authors think?

    • Liz Ginsburg

      Thank you for your comment. I can’t answer on behalf of all the authors but will give you my thoughts and understanding. The ring is felt to be a novel delivery system, and avoids the discharge experienced with suppositories and gel. I would point out that in the large randomized trial by Yanuspolsky et al in our group, vaginal progesterone (crinone gel) was equivalent to IM prog when started 2 days later, but resulted in lower pregnancy rates that IM prog when used in cryo cycles if started at the same time as IM progesterone. My suspicion is that different progesterone formulations result in different delivery rates and target tissue (ie endometrial levels) and that it’s not valid to lump all vaginal formulations together.

  • Juan Giles

    Excellent article. Introduction is well presented, clear and concise, showing a brief background on the subject and defining clearly the aim of the study. The Materials and Methods section describes with great rigour the
    design and methods followed across the study.
    In the Results section, the outcome of each of the endpoints of the study is perfectly detailed, supported on Tables and figures properly.
    As the manuscript showed progesterone vaginal ring provide similar results as daily vaginal gel without differences in security. The advantages: adherence to the treatment (weekly dosing) and probably more comfortable for the patient. We hope to have it soon available in our country with a good price.

    • Liz Ginsburg

      It’s not available here yet either, but it appears to work well in fresh IVF cycles. I am hesitant to directly extrapolate to use in cryopreserved embryo transfer cycles, however, given our recent publication on crinone gel in CET cycles

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