Table 6

Research gaps for home-based ovulation predictor kits (OPKs)

Clinical, programmatic, values-based or human rights question		Current WHO recommendation	Strength of recommendation	Source or quality of evidence	Key GER considerations	Ideal study design(s)	Feasibility and practical constraints	Alternative study design	Main methodological issues arising in the alternative study design
Benefits versus harms	PICO: should home-based OPKs be made available as an additional approach to fertility management for women and couples desiring pregnancy?	Home-based OPKs should be made available as an additional approach to fertility management for women and couples desiring pregnancy.	Strong.	Very low.	No data from LMIC. Key GER considerations include availability and accessibility.	RCT conducted in LMIC with inclusion of outcomes to measure availability and accessibility, and exploration of potential for coercion.	As a strong WHO recommendation, it would be unethical to repeat an RCT of the effectiveness of the intervention.	Prospective non-controlled cohort study to be conducted in several LMIC where the intervention is or will be implemented. Analysis to combine quantitative survey supplemented with focused in-depth qualitative interviews with women and partners to explore GER outcomes of availability and accessibility. Exploration of potential for coercion would be advantageous to determine potential harms. Cost analyses can be nested in the cohort study.	Confounding: participants in cohort self-select to use OPK and may have other similar characteristics that may influence their ability to access OPKs. Measurement bias: self-reporting bias an issue for qualitative component as well as social desirability bias if both the women and partners are included. This will require well trained researchers and validated tools. The triangulation of the qualitative data with the quantitative survey results provides an element of additional validation of outcomes.
	How prevalent is infertility in low-income and middle-income settings and what are the consequences?	Not applicable.		GDG.	Not applicable.	Cross-sectional survey of women from general population in LMIC to ascertain self-reported prevalence of infertility. Cross-sectional semen analysis survey of selected young male populations in LMIC (eg, soldiers) to ascertain male infertility.	A large general population survey is feasible but has cost implications to achieve a sufficiently large sample to be representative.	Focused cross-sectional study of women attending primary care clinics, excluding antenatal care, to ascertain self-reported prevalence of infertility.	Berkson’s bias: people who present with one condition are more likely to have a second condition. Therefore, sampling from a clinic may over-represent the prevalence of infertility and not be representative of the general population.
	What is the impact of using a home-based OPK on communication between partners?	Not applicable.		GDG.	Privacy and confidentiality.	Pharmacy-led survey of women's experiences of partner communication when purchasing the OPK and after using the OPK.	Privacy and perception of lack of privacy, may compromise the integrity of the data and women's willingness to consent to participate. Lack of trained professionals in the pharmacy may also reduce the uptake and quality of the survey.	Qualitative key informant interviews of couples invited to participate either at infertility clinics or at pharmacies.	Social acceptability bias: this study will require careful interviewing with highly trained interviewers to elicit responses that are truthful and not socially desirable. Interviewing women and men separately may reduce this but consequently reduces the observation of communication patterns between partners.
Values and preferences	What are the values and preferences of women and men regarding infertility in settings of deprivation (both in high-income countries and in low-income and middle-income countries)?	Not applicable.		GDG.	Non-discrimination.	Online global cross-sectional survey of men and women delivered through relevant organisations. The participants can be any age and infertility is not an inclusion criteria.	In many settings of deprivation, and especially in LMIC, online accessibility is limited by costs, inadequate technology and lack of knowledge on how to use tools. Specific groups, for example, trans men, may not be reached by a survey aimed at the general population.	Focus groups in purposively sampled populations and regions. Focus groups are most suitable to drive conversations and elicit responses among participants with shared lived experiences and is less confrontational as the aim is not to gather in-depth personal experiences of infertility, but assess current cultural and social norms. Recruitment of specific groups, for example, trans men, can be targeted appropriately.	Social acceptability bias: given that experiences are shared in a group, there may be a reluctance to disclose stigmatising behaviours; however, development of semistructured interview questions in consultation with researchers and representatives of the sampled population to best reflect local beliefs for interrogation can reduce this bias. In addition, a skilled focus group leader can create a safe space for disclosure.
Resource use	Are home-based OPKs cost-effective compared with other fertility management options?	Not applicable.		GDG.	Availability and accessibility.	Modelling studies of cost-effectiveness.	This is a feasible study design. Modelling will require identification of secondary data on the costs of OPK and other fertility management options in a specific country setting. Assumptions underlying the model will include selection of a primary outcome (pregnancy or live birth) or disability-adjusted life years or quality-adjusted life years (which can capture reduced disability or improved quality of life from reduction in anxiety). Assessment and incorporation of human rights measurements such as privacy and non-coercion will be challenging. Any modelling will either need to be country-specific or stratified by country.		Lack of generalisability: a cost comparison would provide indirect data for many regions where differences between costs of fertility management options and costs of access to healthcare differ widely.

GDG, Guideline Development Group; GER, gender, equity and human rights; PICO, Population, Interventions, Comparison and Outcomes; RCT, randomised controlled trial.