In 2005, the Clinical Effectiveness Unit (CEU) of the then Faculty of Family Planning and Reproductive Health Care adopted the World Health Organization (WHO) ‘missed pills’ guidance (Figure 1).1 Many clinicians criticised this change2,–,5 as these new rules appeared to be complex and caused confusion at the grass roots level.6,–,8 There were also concerns that liberalising the ‘missed pills’ guidance (Box 1)9 would lead to additional unplanned pregnancies among pill-takers and did not support safer sex messages or the importance of correct and consistent pill-taking.2 3 5

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Figure 1

Advice from 2005 for women missing combined oral contraceptives (30–35 µg and 20 μg ethinylestradiol formulations).1

Unfortunately the 2005 changes appeared to have been based on old papers since superseded.10,–,16 Even at that time there was evidence contradicting a relaxing of the rules.17,–,19 The CEU admitted they did not consider recently published evidence from 2003 and 2004,10 which was worrying as Pierson et al.19 demonstrated presumed ovulation in 13–19% of 30–35 μg triphasic pill-users following a 3-day dosing error thereby extending the pill-free interval.

Since then further evidence has been published suggesting that hormone-free intervals of 7 or more days can result in breakthrough ovulations and a significant increase in pill failure.20,–,22 One of the arguments posed suggested that even though studies reported higher ovulation rates, failure had not been linked with the ‘pill-free’ interval10 and these women did not become pregnant. However, it should be pointed out that women taking part in these studies used abstinence or barrier methods when pills were missed. Studies exploring ovarian follicular activity when extending the hormone-free interval include small numbers of women and are not powered to detect wide individual variation.23 Authors of a systematic review in 2006 acknowledged that these studies also gave varied definitions of ‘ovulation’ and this inconsistency questions their methodology.23 Accurate detection of ovulation requires frequent and detailed endocrine and ultrasonic evaluation.

The ‘missed pill’ guidance in combined hormonal contraceptives' Summary of Product Characteristics leaflets is overcautious, particularly if pills are missed mid-packet (Box 1).9 In 2010, the UK's Medicines and Healthcare products Regulatory Agency (MHRA) recognised that there was a need to simplify these rules. The MHRA organised a meeting with representatives from a number of key UK organisations including the Faculty of Sexual and Reproductive Healthcare (FSRH), the FPA (Family Planning Association) and the pharmaceutical industry. The aim was to produce standardised guidance on the starting of combined hormonal contraceptives and on ‘missed pills’, emphasising the need for regular pill-taking and not ‘missing pills’ around the pill-free interval.

The MRHA ‘24-hour missed pill advice’ (Box 2) is clear.24 No action needs to be taken until 24 hours or more has elapsed from the usual ‘pill-taking’ time. If this occurs, anywhere in the packet, the forgotten pill needs to be taken and the next pill when it is due – this may mean taking two pills in 1 day. No additional contraception is required.

If two or more pills are forgotten (more than 48 hours late) only the last ‘forgotten’ pill is taken and the next pill taken at the usual time – this may mean taking two pills in 1 day. Additional contraception is needed for the next 7 days. If there are fewer than seven pills left in the pack, the pack should be finished and a new pack started the next day missing out the break.

The ‘emergency contraception (EC)’ advice, however, is confusing. The MHRA suggest that only women “who have unprotected sex in the previous 7 days and have missed two or more pills in the first week of their pack” should seek advice about EC. What about those who have repeated unprotected sex from the start of the hormone-free interval? They could still receive EC. Improved wording would read that “women who have unprotected sex during the hormone-free interval or in the first week of pill taking AND have missed two or more pills in that first week should seek advice about emergency contraception”.

True pill failures still occur and recent data suggest that a standard 7-day hormone-free break is too long for a small number of women.22 25 Six years after the publication of the WHO ‘missed pill’ guidance26 and CEU adoption of these rules a seminal paper has been published that clearly demonstrates the importance of the hormone-free interval for contraceptive efficacy. The International Active Surveillance of Women Taking Oral Contraceptives study in the USA followed 52 218 women prospectively in a controlled, non-interventional manner.20 The aim was to analyse contraceptive failure in those taking oral contraceptives. Total oral contraceptive exposure was 73 269 woman-years and a total of 1634 unintended pregnancies occurred. On closer examination, only 229 (14%) of these pregnancies arose in women who reported that they had taken their pills as directed. In answer to a direct query, the study authors have also reported that ‘non-perfect’ use was most frequent among adolescents.27 When studying women of all age groups, those taking a 24-day regimen containing a progestogen with a long half-life were less likely to have an unplanned pregnancy compared with those taking a conventional 21-day regimen. The adjusted hazard ratio was 0.7 (95% CI 0.6–0.8). Importantly, this reduction of contraceptive failure was even more pronounced in adolescents.27 This ‘real life’ study of pill-users demonstrates the dangers of the hormone-free interval and points the way to further research into more flexible pill regimens where hormone-free intervals are decreased and overall efficacy improved.