Revisiting the fertile window Ovulation occurs on 1 day during each menstrual cycle (even if multiple follicles are involved), and the several days preceding ovulation are when intercourse is most likely to result in pregnancy. Collectively, the potentially fertile days up to and including the day of ovulation are called the ‘‘fertile window’’ (1). Since the 1930s, several biomarkers of the fertile window have been investigated for the purposes of empowering women and couples seeking to use fertility-awareness based methods or natural family planning to avoid pregnancy, as well as to expand understanding of human reproductive physiology. These biomarkers include calendar calculations informed by previous cycle lengths, basal body temperature, cervical fluid (mucus), self-palpation of the cervix, and devices used at home to measure reproductive hormones in the urine, including LH and estrogen or P metabolites (2). In more recent years, there has been greatly increased interest of women and couples in identifying the fertile window for the purpose of conceiving. To appreciate the high level of interest, one need only search for smartphone apps that promise to help a woman track her cycles and identify the days when she can best try to get pregnant. Unfortunately, very few of these apps have published evidence from peerreviewed science. The consumer has to guess which apps most accurately reflect a reasonable scientific base. It may not necessarily be the ones with the most engaging user interfaces, the most compelling marketing messages, or the most popular within social networks. In this context, the analysis by Ecochard et al. represents an important contribution towards understanding the optimal evidence-based use of biomarkers by women and couples trying to conceive. They report that identifying specific characteristics of women's own observations of their cervical fluid, made externally at the vulva 2–3 times per day, can optimize both specificity and sensitivity for identifying on which days of the menstrual cycle intercourse should have the highest probability of resulting in pregnancy (3). To appreciate the importance of specificity as well as sensitivity, consider two theoretical algorithms, based on unspecified biomarkers, to identify the fertile window. Algorithm A identifies a window starting 8 or more days before ovulation and extending to 3 or more days after ovulation, for a total of 12 days or more. This algorithm, similar to Figure 2A in Ecochard et al., has very high sensitivity but low specificity. It identifies the entire fertile window but includes additional false-positive days as well; thus any given positive day has a low likelihood of being a true positive with regard to the days with the highest potential for pregnancy. In contrast, consider algorithm B, which identifies the two or three days before to ovulation as well as the day of ovulation. This algorithm has high sensitivity and also high specificity for the days with the highest potential for pregnancy, similar to Figure 2C in Ecochard et al. (3). Which characteristics of cervical fluid, observed at the vulva, yield a specific and sensitive algorithm for the day of ovulation and the few preceding days? Ecochard et al. used any days in which women identified mucus with a ‘‘wet,
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slippery sensation with or without the appearance of clear, stretchy mucus (similar to a raw egg white),’’ characteristics that identify estrogenic mucus or ‘‘peak mucus.’’ These characteristics reflect rising estrogen levels before ovulation and facilitate sperm survival, storage, and transport at the time of ovulation (2). It is important to recognize that the mucus need not have all of these characteristics of sensation or appearance to qualify, for example, it need not necessarily resemble raw egg white. In their evaluation, Ecochard et al. chose time frames of either 1 day or 5 days before the day of ovulation, but the same principles would apply to intermediate time frames including the most fertile days, that is, the 2 or 3 days before ovulation. The value of this study includes the gold standard reference of serial transvaginal follicular ultrasound to identify ovulation, corroborated by laboratory urinary hormone assays (adjusted for creatinine concentration), in addition to the participant observations of cervical mucus and basal body temperature. These results add to a growing body of evidence that women's observations of their own cervical mucus are an effective and accurate tool for identifying the days of their cycle when intercourse is most likely to result in pregnancy, as well as the occurrence and timing of ovulation. Nevertheless, some questions remain. What kind of instruction and guidance is necessary or sufficient for women to make these observations effectively, and what proportion of women will do so successfully? These data were collected from experienced users of fertility-awareness methods, who had been originally trained by teachers of natural family planning, but our recent work has suggested that many women can learn to observe cervical mucus to identify ovulation on the basis of a written or electronic brochure (4). Further, in light of the compelling physiological link between cervical mucus and natural fertility, and observational data supporting the positive impact of mucus checking on shorter time to pregnancy (1), we need more robust data from randomized trials to assess how much women's observations of their fertile window may shorten time to pregnancy, particularly among couples with subfertility (5). Randomized trials should test systematic observations of cervical fluid at the vulva against one or more other approaches commonly used by couples trying to conceive: urine LH tests, calendar calculations, and/or advice to have consistent intercourse 2–3 times per week. On the basis of the results of this work and other studies, it is reasonable to advise women and couples that observing the estrogenic or peak qualities of cervical fluid at the vulva will identify the days when intercourse is most likely to result in pregnancy, as well as the approximate timing of ovulation itself. The full assessment of the impact of that knowledge for subfertile couples seeking to conceive awaits future randomized trials. Joseph B. Stanford, M.D., M.S.P.H. Departments of Family and Preventive Medicine and Obstetrics and Gynecology, University of Utah, Salt Lake City, Utah
VOL. 103 NO. 5 / MAY 2015
Fertility and Sterility® http://dx.doi.org/10.1016/j.fertnstert.2015.02.015 You can discuss this article with its authors and with other ASRM members at http://fertstertforum.com/stanfordj-fertile-window/
REFERENCES 1. 2. 3.
Use your smartphone to scan this QR code and connect to the discussion forum for this article now.* * Download a free QR code scanner by searching for “QR scanner” in your smartphone’s app store or app marketplace.
VOL. 103 NO. 5 / MAY 2015
4.
5.
American Society for Reproductive Medicine. Optimizing natural fertility: a committee opinion. Fertil Steril 2013;100:631–7. Stanford JB, White GL, Hatasaka H. Timing intercourse to achieve pregnancy: current evidence. Obstet Gynecol 2002;100:1333–41. Ecochard R, Duterque O, Leiva R, Bouchard T, Vigil P. Self identification of the clinical fertile window and the ovulation period. Fertil Steril 2015;103:1319–25. Porucznik CA, Cox KJ, Schliep KC, Stanford JB. Pilot test and validation of the peak day method of prospective determination of ovulation against a handheld urine hormone monitor. BMC Womens Health 2014;14:4. Thijssen A, Meier A, Panis K, Ombelet W. ‘‘Fertility awareness-based methods’’ and subfertility: a systematic review. Facts Views Vis Obgyn 2014;6:113–23.
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slippery sensation with or without the appearance of clear, stretchy mucus (similar to a raw egg white),’’ characteristics that identify estrogenic mucus or ‘‘peak mucus.’’ These characteristics reflect rising estrogen levels before ovulation and facilitate sperm survival, storage, and transport at the time of ovulation (2). It is important to recognize that the mucus need not have all of these characteristics of sensation or appearance to qualify, for example, it need not necessarily resemble raw egg white. In their evaluation, Ecochard et al. chose time frames of either 1 day or 5 days before the day of ovulation, but the same principles would apply to intermediate time frames including the most fertile days, that is, the 2 or 3 days before ovulation. The value of this study includes the gold standard reference of serial transvaginal follicular ultrasound to identify ovulation, corroborated by laboratory urinary hormone assays (adjusted for creatinine concentration), in addition to the participant observations of cervical mucus and basal body temperature. These results add to a growing body of evidence that women's observations of their own cervical mucus are an effective and accurate tool for identifying the days of their cycle when intercourse is most likely to result in pregnancy, as well as the occurrence and timing of ovulation. Nevertheless, some questions remain. What kind of instruction and guidance is necessary or sufficient for women to make these observations effectively, and what proportion of women will do so successfully? These data were collected from experienced users of fertility-awareness methods, who had been originally trained by teachers of natural family planning, but our recent work has suggested that many women can learn to observe cervical mucus to identify ovulation on the basis of a written or electronic brochure (4). Further, in light of the compelling physiological link between cervical mucus and natural fertility, and observational data supporting the positive impact of mucus checking on shorter time to pregnancy (1), we need more robust data from randomized trials to assess how much women's observations of their fertile window may shorten time to pregnancy, particularly among couples with subfertility (5). Randomized trials should test systematic observations of cervical fluid at the vulva against one or more other approaches commonly used by couples trying to conceive: urine LH tests, calendar calculations, and/or advice to have consistent intercourse 2–3 times per week. On the basis of the results of this work and other studies, it is reasonable to advise women and couples that observing the estrogenic or peak qualities of cervical fluid at the vulva will identify the days when intercourse is most likely to result in pregnancy, as well as the approximate timing of ovulation itself. The full assessment of the impact of that knowledge for subfertile couples seeking to conceive awaits future randomized trials. Joseph B. Stanford, M.D., M.S.P.H. Departments of Family and Preventive Medicine and Obstetrics and Gynecology, University of Utah, Salt Lake City, Utah
VOL. 103 NO. 5 / MAY 2015
Fertility and Sterility® http://dx.doi.org/10.1016/j.fertnstert.2015.02.015 You can discuss this article with its authors and with other ASRM members at http://fertstertforum.com/stanfordj-fertile-window/
REFERENCES 1. 2. 3.
Use your smartphone to scan this QR code and connect to the discussion forum for this article now.* * Download a free QR code scanner by searching for “QR scanner” in your smartphone’s app store or app marketplace.
VOL. 103 NO. 5 / MAY 2015
4.
5.
American Society for Reproductive Medicine. Optimizing natural fertility: a committee opinion. Fertil Steril 2013;100:631–7. Stanford JB, White GL, Hatasaka H. Timing intercourse to achieve pregnancy: current evidence. Obstet Gynecol 2002;100:1333–41. Ecochard R, Duterque O, Leiva R, Bouchard T, Vigil P. Self identification of the clinical fertile window and the ovulation period. Fertil Steril 2015;103:1319–25. Porucznik CA, Cox KJ, Schliep KC, Stanford JB. Pilot test and validation of the peak day method of prospective determination of ovulation against a handheld urine hormone monitor. BMC Womens Health 2014;14:4. Thijssen A, Meier A, Panis K, Ombelet W. ‘‘Fertility awareness-based methods’’ and subfertility: a systematic review. Facts Views Vis Obgyn 2014;6:113–23.
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