ii. Summary of evidence and considerations for the new recommendation
The WHO Guideline Steering Group (SG) determined to examine self-administration of injectable contraception as an additional approach to delivering injectable contraception. The PICO question was: For individuals of reproductive age using injectable contraception, should self-administration be made available as an additional approach to deliver injectable contraception? A systematic review was conducted of peer-reviewed journal publications in any location or language. The included studies on people using injectable contraception compared those who had the option of self-administration with those who did not have that option (i.e. the latter all received provider-administered injectable contraception). The studies measured one or more of the following outcomes: unintended pregnancy; side-effects or adverse events (e.g. bleeding, skin-site reactions, mental health); uptake of injectable contraception (initial use); continuation rate of injectable contraception (or, conversely, discontinuation); self-efficacy, knowledge and empowerment; and social harms (e.g. coercion, violence, psychosocial harm, self-harm), and whether these harms were corrected or had redress available (see Annex 6 for further details on the PICOs). More information on the review methods and findings can be found in the published review (12).
Results
The systematic review included six studies, published between 2012 and 2019, with a combined total of 3851 participants: three randomized controlled trials (RCTs) and three controlled cohort studies. Locations included Malawi, Scotland, Senegal, Uganda (one study each) and the United States of America (USA; two studies). Self-injection of DMPA-SC was compared to provider-administered DMPA-SC (three studies) or provider-administered DMPA-IM (three studies), with injections being every three months (12–13 weeks), with some leeway for early and late injections. All the studies followed the participants through 12 months of contraceptive coverage and measured continuation (or discontinuation) of injectable contraception.
Meta-analysis reported in the review found higher rates of continuation with self-administration of injectable contraception compared with provider administration both in the three RCTs (RR: 1.27, 95% CI: 1.16–1.39) and in the three controlled cohort studies (RR: 1.18, 95% CI: 1.10–1.26). Four studies reported pregnancies: meta-analysis showed no difference in this outcome across study arms. Four studies reported side-effects/adverse events: two controlled cohort studies showed increased injection-site reactions with self-administration, but no other side-effects increased with self-administration. One study reported no difference in social harms. No studies measured the outcomes of initial uptake or self-efficacy/empowerment.
Overall, moderate-certainty evidence from the three RCTs indicates that self-administration of injectable contraceptives probably increases continuation of injectable contraception, but is probably equivalent with respect to rates of unintended pregnancy, side-effects/adverse events (except perhaps injection-site pain or irritation) and social harms. Evidence from the three observational studies was consistent with these findings. There were no clear differences in outcomes for different populations (12).
Certainty of the evidence for the recommendation
The available evidence was of moderate certainty overall.
Rationale for the strength and direction of the recommendation
A strong recommendation was made in favour of the intervention, with every GDG member who offered an opinion saying that benefits outweighed any potential harms. The GDG emphasized in the wording of this recommendation that the intervention should be made available as an additional approach, because nobody should have to self-inject due to having no access to provider-administered injections.
Resource use
There was evidence that longer-term contraceptive use is cost-effective for the end-user, but higher initial investment by the health system is required for the provision of training and support/supervision. A study in Uganda reported incremental costs at the start, leading to higher continuation rates and lower rates of unintended pregnancy, indicating that the intervention was quite cost-effective, and would also be cost-saving (13, 14).
Feasibility
All GDG members agreed that this recommendation is feasible.
Equity and human rights
The GDG agreed that, despite insufficient information, there is potential for this self-care intervention to improve equity if implemented in the context of an enabling environment. An enabling environment, however, may be lacking if literacy levels are low and there are barriers to education that may decrease access to the intervention. The GDG noted that the need for contact with a health-care provider before using this intervention means that there may still be a risk of discrimination. More information and evidence is needed on structural and regulatory issues, and on how best to implement this intervention without increasing inequity.
Acceptability of the intervention: values and preferences of end-users and health-care providers
A review was conducted to gather evidence on values and preferences related to this intervention as input for the development of a recommendation on this intervention for this guideline. The review included 14 studies: three used qualitative methods and 11 used quantitative or mixed methods. Two of the included studies were among adolescents and 12 were among the general female population; no studies were found on the values and preferences of providers or other stakeholders. Among the 14 studies, six took place in high-income countries (two in Scotland; four in the USA), one in an upper-middle-income country (Brazil), and seven in low-income countries (one in the Democratic Republic of the Congo; one in Ethiopia; two in Malawi; one in Senegal; two in Uganda). The evidence suggested that women generally like self-administration, find it easy to use, and often prefer it to provider administration. Benefits included saving time and money, ease of administration, and convenience. Barriers included fear of needles, fear of incorrect administration, or preference for seeing a health-care professional.
As described in Chapter 1, section 1.9, a Global Values and Preferences Survey (GVPS) was also conducted among health-care providers and potential end-users on their values and preferences in relation to this and other interventions covered by new recommendations in this guideline. The relevant findings from the GVPS are presented in the box below. Overall, more than 60% of potential users said they had heard of this intervention, and many reported that convenience, access and privacy would be reasons for using it. Most said they would go to a doctor/clinic to obtain supplies for self-administration. The top two concerns reported by health-care providers were safety (e.g. side-effects) and incorrect use by patients.
The GDG reviewed the evidence on values and preferences of potential end-users, and noted that convenience of access was important to them, but there was insufficient evidence from potential users from a range of different subgroups (i.e. vulnerable individuals, different age groups). The GDG concluded that the values and preferences of the potential end-users were variable, and that the nature of the barriers may be easy to overcome.
The GDG noted that while there were limited data on health-care providers’ perspectives, providers generally aim to offer the best possible care to their patients. Health-care providers in low-resource settings may find the option to task-shift the administration of injectable contraception to clients themselves acceptable, as long as effective training can be provided and the safety of users can be assured. Private-sector health-care practitioners, however, may be resistant to self-care interventions due in part to possible financial loss. Acceptability to health-care providers likely also differs by provider age, and level of confidence and/or training. In summary, the GDG concluded that acceptability to health-care providers was uncertain, noting reticence, but also noting that task shifting is achievable with training.
Global Values and Preferences Survey (GVPS) Findings on Self-Administration of Injectable Contraception
End-users and potential end-users
Respondents were asked about their knowledge and use of self-injectable long-acting contraceptives. While more than half of respondents (62.8%, n=486) reported knowing what self-injectable long-acting contraceptives were, less than 5% of respondents reported that they or their partner had ever used this intervention. Among participants who responded to a question on factors that would be important in choosing to use self-injectable long-acting contraceptives (n=420), respondents selected factors including: convenience (51.9%), accessibility (47.6%) and privacy and confidentiality (40.5%). Not feeling judged (23.6%) and feeling empowered (24.8%) were also identified as important factors in choosing to use self-injectable long acting contraceptives. There were no statistically significant differences by residing in the Global North/Global South with regard to awareness of self-injectable long-acting contraceptives. However, participants in the Global North were significantly more likely to report accessing this intervention from a doctor or at a health clinic than those in the Global South. Participants below 50 years old were more likely to have heard of and used self-injectable long-acting contraceptives than those aged 50 and above. Furthermore, the qualitative findings from responses to the open-ended questions highlight acceptability of self-injectable long-acting contraceptives along with the need to provide users with information and guidance.
The largest proportion of respondents 47.7% (n=297 out of 622 responding about this intervention) indicated that they would go to the doctor or health clinic to access supplies for self-administration of injectable contraception. Other respondents reported that they would access it a pharmacy (17.7%; n=110), that they did not know where to get this (12.7%; n=79), that they would buy it online (1.6%; n=10), and that they did not need this intervention (30.2%; n=188). For those who responded about where they accessed information on self-injectable long-acting contraceptives (n=436), 64% (n=279) asked their doctor or health-care provider, 40.8% (n=178) went online, 15.4% (n=67) asked friends or community members, and 17.7% (n=77) reported not having received information on this intervention.
Health-care providers
When the health-care provider respondents of the GVPS were asked whether they had ever provided a referral for self-injectable contraceptives, of those who responded (n=325), more than one-third (41.2%, n=127) indicated they had, 28.2% (n=87) had not, 11% (n=34) responded that the intervention is not available where they live, and 20.8% (n=64) reported that it was not related to their job. When asked about their level of confidence and knowledge on self-injectable long-acting contraceptives, of those who replied (n=296), more than half of respondents (52.4%; n=155) felt confident and informed. One-third (33.1%, n=98) needed more information and one-fifth (21.3%, n=63) needed training to provide this service.
Among participants who reported concerns regarding this intervention (n=229), 52% (n=119) indicated safety concerns, 47.2% (n=108) indicated concerns of misuse by patients, 40.2% (n=92) reported concerns that a patient would not access needed health care, and 21% (n=48) indicated concerns about the quality of products. Of those who responded about benefits of self-injectable contraceptives (n=224), 68.8% (n=154) indicated the benefit of convenience, 48.2% (n=108) indicated it is empowering, 44.6% (n=100) indicated reduction of health care workload, 35.3% (n=79) indicated removal of barriers, and 30.8% (n=69) indicated that it is cheaper for the client.
New recommendation on self-management of contraceptive use with over-the-counter oral contraceptive pills (OTC OCPs)
- REC 11 (NEW)
Over-the-counter oral contraceptive pills (OCPs) should be made available without a prescription for individuals using OCPs.
(strong recommendation, very low-certainty evidence)
i. Background
Oral contraceptive pills (OCPs), including both combined oral contraceptives (COCs) and progestogen-only pills (POPs), are widely used, safe and effective methods of birth control. Access to OCPs, however, varies around the world. In some countries, OCPs are available over the counter (OTC) – meaning without the need for a prescription; OTC includes (a) “off the shelf” availability with no screening and (b) “behind the counter” pharmacy access requiring eligibility screening by trained pharmacy staff before dispensation. In other countries, there is no OTC access to OCPs at all, such that a prescription from a health-care provider is required. A review of contraceptive access across 147 countries, published in 2015, found that 35 countries had OCPs legally available OTC, 56 countries had OCPs informally available OTC, 11 countries had OCPs available OTC but only after eligibility screening by trained pharmacy staff, and 45 countries required a prescription to obtain OCPs (no OTC access) (15). Given that, globally, an estimated 44% of pregnancies are unintended (16), making OCPs easier to access in more settings by making them available OTC (either “off the shelf” or “behind the counter”) could contribute to increasing OCP use and reducing unintended pregnancies.
ii. Summary of evidence and considerations for the new recommendation
The SG determined that OTC availability of OCPs should be reviewed as one of the topic areas for the development of new recommendations; therefore, a systematic review was conducted on the PICO question: For individuals using oral contraceptive pills (OCPs), should OCPs be made available over-the-counter (OTC), i.e. without a prescription? Peer-reviewed articles published through 30 November 2018 were included if they compared either full OTC (“off the shelf”) or pharmacist dispensation (“behind the counter”) to prescription-only availability of OCPs and measured at least one of the selected outcomes of interest: uptake of OCPs (initial use); continuation of OCPs (or, conversely, discontinuation); adherence to OCPs (correct use); comprehension of instructions (product label); unintended pregnancy, side-effects, adverse events, or use of OCPs despite contraindications; social harms (e.g. coercion, violence, psychosocial harm, self-harm), and whether these harms were corrected or had redress available; and client satisfaction (see Annex 6 for further details on the PICOs). The focus was on daily OCP use for routine pregnancy prevention and so studies examining pills specifically for emergency contraception were not included. Meta-analysis was not conducted due to the small number of included studies (17).
Results
The effectiveness review included four observational studies with a total of 5197 participants, reported in six articles. Two of these studies were published in the 2000s, written up in four articles. One of these was the Border Contraceptive Access Study (a longitudinal cohort study from Texas, USA, which used convenience sampling and was reported in three articles), and the other was the 2000 Mexican National Health Survey (a cross-sectional comparison study, which was reported in one article). Both of these studies compared women who obtained OCPs OTC in Mexico to women who obtained OCPs from providers in either Mexico or the USA. The two other studies were from Bogota, Colombia (1974 Fertility and Contraceptive Use Survey), and from Mexico (1979 Mexico National Fertility and Mortality Study), and were published in the 1970s, providing cross-sectional comparisons of women using OCPs obtained OTC or from a private-sector or national health-care provider. All studies included mainly women using COCs, rather than POPs (with differing pill formulations). The included studies reported on four of the seven outcomes of interest: continuation of OCPs, use of OCPs despite contraindications, side-effects and client satisfaction (17).
With a small evidence base, evidence from one observational study (the Border Contraceptive Access Study) indicated that women who get OCPs OTC may have higher OCP continuation rates over nine months of follow-up compared with women who get them from a clinic (adjusted hazard ratio: 1.58, 95% CI: 1.11–2.26). The two older studies also examined continuation. The Mexican study found no difference between the three groups (57–60% continuation after 12 months). The Colombian study found that after both 12 and 24 months, OCP continuation was approximately 5% higher for clinic users than OTC users.
Evidence from both of the more recent observational studies showed mixed evidence on whether women who get OCPs OTC are more likely to use OCPs despite contraindications. The Border Contraceptive Access Study found OTC users were more likely to report at least one WHO category 3 contraindication (13.4% versus 8.6%, P = 0.006), but not category 4 contraindications. Meanwhile, the analysis of the 2000 Mexican National Health Survey found no differences in contraindicated use. In the meta-analysis, the pooled effect size from these two studies showed higher odds of using OCPs despite at least one category 3 or 4 contraindication among OTC users (OR: 1.57, 95% CI: 1.18–2.09).
Two studies reported on side-effects of OCP use: the longitudinal Border Contraceptive Access Study reported fewer side-effects among OTC users and the Colombian study reported more side-effects among OTC users.
The longitudinal cohort study (Border Contraceptive Access Study) reported on client satisfaction, finding high patient satisfaction with both OTC and prescription access: “three quarters of clinic users and more than 70% of pharmacy users said they were very satisfied with their source … Only about 4% of each group said they were either somewhat or very unsatisfied with their source” (18).
There were no data on initial uptake, correct use, comprehension of instructions, unintended pregnancy, adverse events, or social harms.
Certainty of the evidence for the recommendation
This recommendation was based on very low-certainty evidence. The GDG also noted the potential for bias with self-reporting of side-effects. Both of the more recent studies included in the systematic review found that women who obtained their OCPs OTC were different in at least some sociodemographic characteristics from those who obtained OCPs from clinics, but both studies used analysis methods to appropriately adjust for confounders to address this discrepancy, which the reviewers judged improved the validity of the effect estimates. Meanwhile, the two studies from the 1970s reported only minor sociodemographic differences between the groups, although neither presented supporting data nor adjusted for confounders. The Border Contraceptive Access Study relied on convenience sampling, but was strengthened by its longitudinal design. Conversely, the other three studies were cross-sectional, but were strengthened by their multi-stage sampling strategies (17).
Rationale for the strength and direction of the recommendation
Despite the very low-quality evidence, after extensive discussion, the GDG agreed that the benefits outweighed the harms and a strong recommendation was made in favour of the intervention. The GDG put the emphasis on equity, which is supported by the increased availability made possible by OTC access, and on high feasibility, given that the intervention is already available in many countries. While contraindications are an important concern, research has indicated that women can self-screen for contraindications fairly well using a simple checklist (19). In many parts of the world where OCPs are already available without a prescription, self-screening tools are provided with the OCP packaging. The GDG noted the preference for eligibility screening before initiation of OCPs.
The GDG also noted the need for regular linkages to the health system. In the 35 countries where OCPs are already legally available OTC, with neither prescription nor pharmacist screening required, locally adapted guidance (e.g. from WHO regional offices) could indicate that this approach should continue. The GDG agreed that since OTC availability is associated with higher continuation rates, this intervention should be available, even where health systems are not strong, but that more research is needed on managing contraindications.
In-country systems need to assess the way that OCPs are being made available without prescriptions; there need to be systems in place to ensure that end-users can be accurately screened for contraindications, whether that means (i) self-screening using a checklist or other tool available at the point of sale, or (ii) being screened by a pharmacist or community health worker. The GDG also noted the need to be aware that many OTC drugs, potentially including OCPs, are counterfeit, off-label and/or contain toxic components. The quality of all drugs needs to be regulated to a high standard, but this issue is beyond the scope of these guidelines.
Resource use
The GDG agreed that this intervention is cheap in many places, noting that government subsidies should be retained if distribution is transferred to an OTC approach. The GDG expressed concerns that the burden of payment may fall to end-users themselves if insurance does not cover OTC availability, thus risking a decrease in accessibility. On the other hand, this intervention could be cost-saving for end-users as they will not have to pay to see a doctor, travel to a clinic or take time off work (and lose wages) for a clinic appointment. The resource implications for this intervention would be context specific, depending on current systems, costs and the burden of payment.
Feasibility
The GDG agreed that the intervention is feasible, given that it is already in use in several countries.
Equity and human rights
The GDG agreed that this intervention is likely to increase access and reduce discrimination (supporting human rights), especially among adolescent girls and young women and sexual and gender minorities, since it may remove the need to see a health-care provider and/or to get third-party authorization from a parent or spouse. Attention to context is important, however, as in some countries OCPs may not be sold to unmarried individuals. Furthermore, increased access could perhaps be accompanied by a decrease in quality of care.
Acceptability of the intervention: values and preferences of end-users and health-care providers
The systematic review for this PICO (17) included a review of 22 quantitative and qualitative studies (reported in 23 articles) on the values and preferences relating to OTC access to OCPs (including behind-the-counter pharmacy access) among current and potential users and women in general (13 articles); health-care providers and pharmacists (eight articles); the general public (one article); and a combination of women and health-care providers (one article). Nearly all the studies were conducted in the USA, while one each was conducted in Canada, France and the Republic of Ireland. Regarding full OTC (off-the-shelf) access to OCPs, the evidence indicated that users/potential users generally favoured this, citing ease of access, convenience, privacy and time saved by avoiding clinic visits for presciptions. Concerns of users included cost, continued use of preventive care/screening (e.g. Pap smears, breast exams, STI screening), and the safety of OTC access, especially for young people. Health-care providers were moderately supportive of full OTC access, expressing concerns including safety, efficacy, correct use and missed examinations for medical contraindications. Regarding OTC pharmacy (behind-the-counter) access, users also generally favoured and were satisfied with this, citing increased access and convenience. Pharmacists were generally very supportive of this approach while physicians were only moderately supportive. In general, providers were also more supportive of providing POPs OTC (behind the counter) compared with COCs. Potential barriers to this OTC pharmacy access included: safety, time constraints, lack of private space in the pharmacy, increased liability, and reimbursement. Overall, support was generally higher for OTC dispensation in pharmacies (behind the counter) compared with full OTC availability (off the shelf).
As described in Chapter 1, section 1.9, a Global Values and Preferences Survey (GVPS) was also conducted among health-care providers and potential end-users on their values and preferences in relation to this and other interventions covered by new recommendations in this guideline. The relevant findings from the GVPS are presented in the box below. Overall, almost all potential end-users who responded said they had heard of this intervention, and the most important factors affecting uptake were access, convenience, and privacy and confidentiality. Most said they would access the intervention through a doctor or health clinic. When responding health-care providers were asked about this intervention, the top two concerns reported were misuse by patients and safety (e.g. side-effects).
The GDG reviewed the evidence from the systematic review and the GVPS and concluded that overall there was minor variability in the values and preferences of potential end-users, and also minor variability in acceptability among health-care providers in relation to the intervention. The GDG noted that the data were from high-income countries where there may be resistance to this intervention due to health system issues surrounding insurance and reimbursement. This intervention is already in practice in many countries around the globe. More data are needed from drug stores and informal pharmacies, as well as from lower-cadre health workers and non-health professionals.
Global Values and Preferences Survey (GVPS) Findings on Access to OCPs
End-users and potential end-users
Of the GVPS respondents who reported whether or not they had heard of OCPs (n=783), 0.9% (n=7) reported not knowing what they are, 3.6% (n=28) reported that they knew what they were but they did not know how to access them, and 95.5% (748) reported that they both knew what they were and where to access them. When asked about their use of OCPs, approximately half of respondents (n=720) indicated that they or their partner had used oral contraceptives: 43.6% (n=314) had used them in the past, 6.8% (n=49) had used them within the past three months, 26.5% (n=191) had not used OCPs, and 23.1% (n=166) did not have a need for contraception. The most important factors related to OCP uptake, as reported by 513 respondents, were access (57.1%, n=293), convenience (56.3%, n=289) and privacy and confidentiality (46.4%, n=238). The possibility that OCPs can reduce the feeling of being judged (24.2%, n=124) and can foster a sense of empowerment (28.8%, n=148) were also listed as important factors associated with uptake.
There were no statistically significant differences in awareness of OCPs between respondents residing in the Global North versus the Global South. However, participants residing in the Global North were more likely to report using OCPs than those in the Global South. Those in the Global South were more likely to report accessing OCPs from a pharmacy, while those in the Global North reported being more likely to access OCPs from a doctor or a health clinic. Participants aged 50 and above were more likely to have heard of OCPs. There were no other differences in responses by place of residence, age or gender.
Participant responses related to OCPs in the open-ended (qualitative) survey responses revealed that OCPs were perceived as simple enough, compared to other interventions (e.g. abortion self-management), that using OCPs would not require the direct assistance of a health-care provider, and that OCPs should be made freely available. Concerns expressed regarding OCPs were focused more on the delivery and availability, as opposed to the intervention itself. Participants also discussed challenges with the care they received from health-care providers when accessing OCPs. Taken together, the qualitative responses reveal great promise for over-the-counter (OTC) access to OCPs in allowing individuals to circumvent health-care providers who may stigmatize certain groups of OCP users. At the same time, providing instructions and contraindications for use of OCPs in an accessible language and format for people of various literacy levels is another implementation consideration.
Among respondents on this topic and for this intervention (n=658), 56.5% (n=372) would access OCPs through a doctor or health clinic and 45.4% (n=299) would access them through a pharmacy. Very few indicated online sources (2.7%; n=18) or not knowing where to get this intervention (0.5%; n=3). Nearly one fifth (18.8%; n=124) indicated not having a need for OCPs. Of the individuals who reported accessing information on OCPs (n=496), 76.2% (n=378) asked a doctor or health-care provider, 51.2% (n=254) went online, 24% (n=119) asked friends and community members, and 4.8% (n=24) have not received information on this.
Health-care providers
When asked about referrals for use of OCPs, of the health-care providers who responded (n=325), about three quarters (74.8%; n=243) reported having provided a referral, 6.8% (n=22) had not, nearly one fifth (18.5%; n=60) indicated it was not relevant to their job and one person (0.3%) indicated it is not available where they live. Out of respondents on this question (n=316), most said they feel confident and informed about OCPs (82.3%; n=260). There were 11.4% (n=36) of health-care providers who replied that they need more information and 9.2% (n=29) indicated that they need more training in order to provide a referral for OCPs. Of those who indicated their concerns regarding OCPs (n=263), most expressed concerns about misuse by patients (58.6%; n=154) and about safety (53.6%; n=141). Others indicated concerns that patients would not access health care when needed (31.6%; n=83) and concerns about the quality of products (27.8%; n=73). Of those respondents who answered regarding the benefits of OCPs (n=267), three quarters (75.7%; n=202) expressed that OCPs are convenient for the patient or client. Next, 49.8% (n=133) reported that OCPs are empowering, 44.2% (n=118) expressed that they will remove barriers like stigma, 40.4% (n=108) expressed that OCPs will reduce health care workload, and 40.1% (n=107) expressed the OCP use will be affordable.
New recommendation on self-screening with ovulation predictor kits (OPKs) for fertility management
- REC 12 (NEW)
Home-based ovulation predictor kits (OPKs) should be made available as an additional approach to fertility management for individuals attempting to become pregnant.
(strong recommendation, low-certainty evidence)
i. Background
For couples who are attempting pregnancy through coitus, or individuals who are attempting pregnancy through vaginal insemination, knowing when to do so can be difficult. There is a short window during the menstrual cycle when ovulation occurs and a mature egg or eggs have been released and are able to be fertilized by sperm, with subsequent embryo implantation. Reportedly, up to 85% of women will become pregnant on their own within 12 menstrual cycles (20, 21). However, global estimates indicate that 15–25% are unable to become pregnant despite attempting for at least five years (22, 23). Infertility is typically diagnosed if pregnancy has not been achieved after 12 months of regular intercourse without a condom (24), although this timeframe may vary by age and by presence of anatomical abnormalities or disease (25). Individuals who are diagnosed as infertile may turn to medically assisted reproduction (MAR) using various diagnostics and interventions for fertility care (26). However, some options are unaffordable or inaccessible, especially in resource-constrained settings.
Preventing fertile individuals and couples from assuming a status of infertility, when they may be able to help themselves to become pregnant with better knowledge of their reproductive cycles and fertile window, can be empowering and can avoid high costs, especially if there is an ability to prevent recourse to more expensive assisted reproductive technologies. Use of ovulation predictor kits (OPKs) can support better timing of condom-less intercourse or the self-intravaginal insemination during the fertile window. OPKs are readily available in many settings worldwide without the need for a prescription, including at pharmacies, supermarkets and other shops, as well as from websites found online, which can deliver goods anywhere in the world. OPKs do not actually predict ovulation, but rather they predict the surge of luteinizing hormone that precedes ovulation, while also tracking corresponding oestrogen levels (27). The kits do not directly indicate a peak fertility day, and multiple pregnancy attempts may still be needed within the appropriate timeframe. OPKs increase fertility awareness and may alert individuals to potential menstrual cycle abnormalities. Individuals with HIV serodiscordant partners could use OPKs to time intercourse and limit exposure to condom-less sex in order to reduce the risk of transmission of HIV and other sexually transmitted infections (28, 29). Single individuals, those who wish to observe specific religious or cultural traditions, migrant/irregular workers, or couples in unconsummated marriages (e.g. due to male erectile dysfunction or physical disabilities) might benefit from using OPKs to appropriately time condomless intercourse or attempt self-intravaginal insemination (30).
ii. Summary of evidence and considerations for the new recommendation
The SG determined that the use of home-based OPKs should be reviewed for the development of this guideline. Therefore, WHO commissioned a new systematic review of available evidence of effectiveness and values and preferences surrounding the use of home-based, self-initiated OPKs for fertility management (31). The PICO question was: For individuals attempting to become pregnant, should home-based ovulation predictor kits (OPKs) be made available as an additional approach for fertility management? To be included in the effectiveness review, studies had to compare individuals who managed their fertility using (commercially available) home-based OPKs with those who had clinician-led assessment only, or no ovulation prediction, and they had to be published in a peer-reviewed journal (through 21 November 2018). Included studies also had to report on at least one of the following outcomes of interest: time to pregnancy; pregnancy; live birth; stress/anxiety; social harms or adverse events (e.g. device-related issues, coercion, violence, psychosocial harm, self-harm, suicide, stigma, discrimination), and whether these harms were corrected or had redress available (see Annex 6 for further details on the PICOs). Inclusion was not restricted by location of the study or language of the publication.
OPKs used in the reviewed studies could include both urine-and serum-based kits and any modality (stick, monitor, digital, electronic slip that connects to a phone, etc.). To focus on OPKs as a specific biomedical and biochemical intervention, the review did not include behavioural and non-biochemical methods of ovulation prediction, such as calendar/standard days/fertility awareness methods, basal body temperature monitoring, Billings/cervical mucus monitoring methods, use of fertility beads, etc. (31).
Results
Four studies were included in the effectiveness (PICO) review: three RCTs and one prospective cohort (observational) study. The four studies included a total of 1487 women (or couples), with individual study sample sizes ranging from 117 to 1000, and with participants’ ages ranging from 18 to 43. The articles were published between 1992 and 2013 and reported on studies taking place between 1991 and 2010. All studies were conducted in high-income countries: Australia, Scotland, the United Kingdom and the USA. Two studies recruited women from the general population nationwide, and the other two recruited women undergoing fertility treatment or investigation. All studies measured pregnancy as an outcome (with follow-up periods ranging from two to six menstrual cycles). Two studies measured time to pregnancy and one study reported on stress/anxiety. None of the studies presented comparative data on live births or social harms/adverse events.
All the included studies reported pregnancy rates. A single RCT from the 1990s among couples with unexplained or male-factor infertility provided uncertain results indicating no difference in clinical pregnancy rate (RR: 1.09, 95% CI: 0.51–2.32). Meta-analysis of two more recent RCTs (conducted in 2001–2002 and 2010) among the general population found higher self-reported pregnancy rates among OPK users (pooled RR: 1.40, 95% CI: 1.08–1.80). Meta-analysis of all three RCTs incidated that using a home-based OPK for timing intercourse was associated with higher rates of pregnancy compared with not using an OPK (pooled RR: 1.36, 95% CI: 1.07–1.73). A small observational study published in 1996 found higher rates of pregnancy with laboratory testing versus OPKs among women using donor insemination services (RR: 0.35, 95% CI: 0.15–0.86).
Two RCTs found that there may be no difference in time to pregnancy.
Results for measures of stress from a single RCT showed mixed results. When stress/anxiety was measured with the Perceived Stress Scale after two menstrual cycles using OPKs, results indicated that there may be no appreciable difference in stress/anxiety (mean difference [MD]: 1.98, 95% CI: −0.91 to 4.87). When stress was measured using the Positive and Negative Affect Schedule (PANAS positive affect scale), results showed there may have been an increase in stress in those using OPKs (MD: −4.51, 95% CI: −8.77 to −0.25).
Certainty of the evidence for the recommendation
This recommendation was based on low-certainty evidence, and a lack of data generated within low- and middle-income countries (LMICs). The risk of bias among the RCTs was generally high. Blinding was not possible for this intervention – all participants knew whether they were in the intervention or control group – increasing the risk of performance bias. The outcome “self-reported pregnancy” may have suffered from detection bias, as lack of blinding could lead to greater awareness of fertility, and increased frequency of pregnancy testing, and thus greater rates of positive pregnancy tests. Increased frequency of intercourse by couples using OPKs is also possible, which may have influenced the outcomes of pregnancy and time to pregnancy. There is also a high risk of publication bias, given the small number and small sample size of the included studies. In addition, two studies were funded by the OPK manufacturer and one study had its intervention delivered by the manufacturer; because of the commercial nature of OPKs, there may be some concern that data yielding negative results have not been published.
Rationale for the strength and direction of the recommendation
After extensive discussion, the GDG made a strong positive recommendation in favour of the intervention, despite the low certainty of the evidence and the fact that it was all from high-income countries. A strong recommendation was made because this intervention provides an additional choice and option for those who are concerned that they may not be attempting pregnancy during the appropriate time frame within the menstrual cycle. Another reason for making a strong recommendation, despite the limited evidence, is that this is a low-cost intervention that would be more likely to be needed in the context of LMICs where other fertility services are unaffordable or not available. But the intention of the recommendation is not to say that individuals or couples should use this intervention (e.g. if the cost is beyond their means). The GDG agreed that the benefits outweigh harms, noting that there are few to no harms if this intervention is provided with appropriate instructions. In addition, if an individual or a couple are unable to become pregnant within six months to one year of attempting during the fertile window, it would be suggested that they seek advice from their health-care provider. They may be advised to either continue trying or be assessed for a potential infertility diagnosis. Since there are so many possible reasons for infertility, the GDG expressed concern about the use of OPKs beyond one year, without this additional suggestion. Although a strong recommendation has been made, it should be noted that there is a clear need for more research in LMICs on this topic, and for a larger review comparing this to other interventions for couples seeking to become pregnant. One GDG member wished their reservations to be noted – that a strong recommendation was not supported by the evidence – but agreed to support the consensus decision.
Resource use
The GDG agreed that the intervention may increase costs and that costs may be borne by the user. It was noted that the cost of OPKs differs widely – from one month’s income on the minimum wage in Egypt to half a day’s income on the minimum wage in the Philippines – and that this may not be affordable. The GDG noted that OPKs seem fairly expensive, even in high-income countries.
Feasibility
The GDG agreed that the intervention is feasible.
Equity and human rights
This intervention has the potential to improve equity, but the GDG noted that there is uncertainty surrounding this reproductive health issue. High cost could limit access (depending on who covers these costs), which may increase inequity. Not being able to build a family through pregnancy may be a challenge for individuals, couples and their families. OPKs have the potential to improve human rights, but also the potential to be harmful if appropriate information is not included with this intervention. As with all interventions related to the decision to, or not to, become pregnant, the gender dimension needs to be carefully assessed: Who is blamed for lack of pregnancy? Who can access the intervention? In poor families where individuals and couples are using the intervention, if a pregnancy does not occur, there could be harm to the individuals (usually the woman) or in some societies even to the family. The GDG noted the potential for harm if there is coercion to use an OPK and that this might be minimized through education for individuals and couples on how the OPK could be used effectively with appropriate referral if pregnancy does not occur.
Acceptability of the intervention: values and preferences of end-users and health-care providers
The systematic review conducted for this topic also included a review of evidence on the values and preferences of end-users of OPKs. Seven articles reporting on six studies were included, all of which involved primary data collection, and the results were summarized qualitatively (31). Almost all end-users reported feeling satisfied with OPKs (i.e. they were viewed as easy to use and understand, convenient, accurate), as well as being comfortable and confident in their ability to use OPKs. They appreciated knowing more about their menstrual cycle and timing to attempt pregnancy, which decreased stress and enabled teamwork with their partner. However, those who do not become pregnant within a short time frame could become overdependent on any method of timing intercourse, including the use of OPKs, which could result in only planned coitus, and could foster obsession and doubt – especially if there is a lack of education or lack of referral to a health-care provider after six months or up to one year of trying. Most participants stated that they would use OPKs again in the future.
The GDG reviewed the evidence from the systematic review and concluded that there was minor variability in the available data on values and preferences among users. The GDG considered that from a consumer perspective, the intervention is viewed as empowering and useful.
Regarding acceptability among health-care providers, the GDG considered, based on their experience, that from a pharmacist perspective, a recommendation from WHO would give them more license to provide this intervention. The GDG concluded that there was minor variability in the acceptability of this intervention among health-care providers.
