Reply of the Authors: Parity and subfertility effects of continuous oral contraceptive on fertility are important

LETTER TO THE EDITOR Reply of the Authors: I would like to thank Drs. Hitchcock and Prior for their insightful letter. Critical review of the scientific literature is necessary, and the discussions that such letters generate are always beneficial. The main point of their letter was the important distinction between return to fertility and the definition of subfertility (or infertility). It is widely recognized and appreciated that the definition of infertility is the inability to achieve a pregnancy in 1 year in the absence of family planning or the use of contraception. It is also recognized that there are limitations to this definition. The American Society of Reproductive Medicine clearly recommends that there are circumstances when evaluation for subfertility should be initiated before 1 year (1). Examples include a suspicion of anatomic or physiologic disorder as well as age of more than 35 years for a woman. Clarification of the natural history of return to fertility after stopping oral contraception and therefore assisting astute clinicians in the decision to reassure a couple or initiate a workup for subfertility was one the goals of this series of publications (2, 3). The decision about when to initiate a workup for subfertility must be individualized based on the age of the woman and the context of the couple’s lives, co-morbidities, and the goals and desires of the couple. Given the small and certainly transient contribution that previous oral contraceptive (OC) pill use appears to contribute, this is unlikely to play a substantial role in the decision of when to intervene. Drs. Hitchcock and Prior raise interesting point regarding the potential confounding effect of parity on return to fertility. I agree that the data suggest there may be a lower rate of fertility for nullparous women at 3 months, which attenuates at 6 months and disappears by 12 months. One must be cautious, however, in overinterpreting the clinical and statistical significance of findings based on a small sample size, in a single trial. In this trial the relative risk for a nulliparous women achieving a pregnancy within 3 months compared with parous women was 0.41 (95% confidence interval [CI] 0.15–1.14), a none statistically significant finding. I hope that Dr. Hitchcock and others will conduct the further research needed to verify or refute this finding. Finally, I wish to address the concern regarding conflict of interest. The study of return to fertility after continuous oral contraception was part of a pharmaceutically sponsored clinical trial, of their own product, for the purposes

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of obtaining Food and Drug Administration approval. This is clearly stated in the article (2). I was one of the many investigators who participated in the pivotal multicenter trial (4). I had full editorial control and received no compensation for preparation of this manuscript. To guard against the unfortunate implicit suggestion that all data collected and analyzed with pharmaceutical support are biased, I elected to present all the data (return to fertility at 3 months, 12 months, and 13 months) to be transparent and complete. An educated reader can draw their own conclusion from objective data. Unintended pregnancy, with a 49% prevalence in the United States, is a major public health problem. It is our responsibility to understand the relative risks and benefits of the contraceptive technologies available so that we can responsibly counsel our patients and maximize healthy pregnancy outcomes. Kurt Barnhart, M.D., M.S.C.E. Director, Women’s Health Clinical Research Center Assistant Dean, Clinical Trial Operations, University Of Pennsylvania School of Medicine, Philadelphia, Pennsylvania June 18, 2009 K.B. was an investigator for this poststudy follow-up and received research funding from Wyeth Research, Collegeville, PA. Other sources of research funding and/or financial relationships include Novo Nordisk (consultant), Johnson; Johnson, Duramed, Xanodyne, Boehringer Ingelheim, Third Wave, Pfizer, and MGI Pharma (investigator).

REFERENCES 1. Practice Committee of the American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss. Fertil Steril 2008;90(5 Suppl):S60. 2. Barnhart KT, Mirkin S, Grubb G, Constantine G. Return to Fertility after Cessation of a Continuous Oral Contraceptive. Fertil Steril 2009;91:1654–6. 3. Barnhart KT, Schreiber CA. Return to fertility following discontinuation of oral contraceptives. Fertil Steril 2009;91:659–63. 4. Archer DF, Jensen JT, Johnson JV, Borisute H, Gs Grubb, Constantine GD. Evaluation of a continuous regimen of levonorgestrel/ethinyl estradiol: phase 3 study results. Contraceptive 2006;74:439–45.

doi:10.1016/j.fertnstert.2009.06.037

Fertility and Sterility Vol. 92, No. 4, October 2009 Copyright ª2009 American Society for Reproductive Medicine, Published by Elsevier Inc.

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