Can in vitro fertilization cycles be salvaged by repeat administration of intramuscular human chorionic gonadotropin the day after failed injection?

This study investigated the incidence of failed hCG administration as evidenced by negative serum β-hCG after initial trigger injection, and the ability to salvage such cycles through repeat administration of hCG before retrieval.

David E Reichman, M.D., Eleni Greenwood, M.S., Laura Meyer, M.D., Isaac Kligman, M.D., Zev Rosenwaks, M.D.

Volume 98, Issue 3, Pages 671-674, September 2012


To investigate the incidence of negative serum hCG after initial IM trigger injection and whether such cycles can be salvaged through repeat administration of IM hCG.

Retrospective cohort study

Academic medical center

All patients undergoing IVF at the Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College from January 1, 2005, to November 1, 2011.

Repeat hCG administration in cases of failed initial trigger

Main outcome measures:
Fertilization, implantation, clinical pregnancy, and live-birth rates were analyzed in the index population as compared to a control population matched for age, year of cycle start, diagnosis, stimulation protocol, number of prior IVF attempts, oocyte yield, and number of embryos transferred.

The incidence of failed initial IM hCG injection was low, occurring in only 0.25% of the 17,298 fresh IVF cycles occurring at our center over the study period. Of the 41 patients undergoing retrieval who received a second IM injection of hCG approximately 24 hours after the first, the live-birth rate was 39.02%. Compared to matched controls, there were no statistical differences in oocyte maturity, fertilization, implantation, clinical pregnancy, or live-birth rates.

While the incidence of failed hCG injection is rare, this study reveals that cycles characterized by incorrect initial administration or failed absorption of hCG can be salvaged by early detection and repeat injection. IVF-ART programs may benefit their patients through the assessment of either urine pregnancy tests or measurement of quantitative serum β-hCG prior to retrieval, thereby preventing empty follicle syndrome.

  • Juan Giles

    Congratulations, I have read
    with great interest your manuscript, in which the efficacy of repeat
    administration of hCG the day after failed injection is analysed.

    I agree with you that
    evaluating the correct absorption of HCG (a crucial step in IVF procedures) is
    a good preventive intervention, in spite of the low incidence of this
    situation. I think that the alternative approach of using urine pregnancy test
    is also interesting, in some situations or for some centres.

    You have shown without doubt
    that repeat administration of hCG the day before retrieval is an effective
    alternative in this group of patients. Moreover, your manuscript contains
    another two interesting points: the etiology resulting from human error in most
    of the cases and that the pregnancy rate is not affected in these situations by
    trend in oestradiol levels.

    In our country, only
    subcutaneous r-hCG is available at present, probably
    decreasing the risk of error in mixing or administering the medication.
    However, we also suffer this problem. Our tendancy is to readministerhCG after
    failing to retrieve oocytes from the first ovary (usually do not pick up all of
    them), in general with good results.

    I would like to know which is
    your protocol in the case of persistent negative serum β-hCG test and your
    opinion about trigger ovulation with GnRH analogues in these patients.

    And lastly, have you seen any
    relation between serum hCG levels the day before retrieval and the number of
    oocytes obtained in the pick up?

  • Micah Hill

    This data is very reassuring both in the low incidence of a negative hCG the day after trigger and in the good outcomes in patients after a rescue dose. Im curious if the authors looked at the outcomes in patients with positive but very low hCG levels the day after trigger (e.g. an hCG of 10, which is positive and doesn’t receive a rescue dose).

    • Zev Rosenwaks

      In this study, we exclusively analyzed cycles in which the serum hcg level was < assay. We are, however, performing a separate study regarding the issue you pose, and hope to have data to report shortly.

      David Reichman MD & Zev Rosenwaks MD

      • Micah Hill

        Thank you Drs. Reichman and Rosenwaks for yor reply and the nice study. I look forward to seeing that data in the future!

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