Fertility-related research needs among women at the margins

Abstract

Abstract

Fertility-related research encompasses fertility intentions, preconception care, research amongst pregnant women, and post-partum outcomes of mothers and children. However, some women remain under-represented within this domain of study. Women frequently missing within fertility-related research include those who are already the most vulnerable to health disparities, including female sex workers, lesbian, gay, bisexual, and transgender women, women living with HIV, and women who use drugs. Yet characterization of the needs of these women is important, given their unique fertility-related concerns, including risks and barriers to care emanating from social stigmas and discrimination. This synthesis provides an overview of fertility-related evidence, highlighting where there are clear research gaps among marginalized women and the potential implications of these data shortfalls. Overall, research among marginalized women to date has addressed pregnancy prevention and in some cases fertility intentions, but the majority of studies have focused on post-conception pregnancy safety and the well-being of the child. However, among female sex workers specifically, data on pregnancy safety and the well-being of the child are largely unavailable. Within each marginalized group, preconception care and effectiveness of conception methods are consistently understudied. Ultimately, the absence of epidemiologic, clinical and programmatic evidence limits the availability and quality of reproductive health services for all women and prevents social action to address these gaps.

Résumé

La recherche relative à la fécondité englobe les intentions en matière de fécondité, les soins avant la conception, la recherche chez les femmes enceintes et l’état post-partum des mères et des enfants. Cependant, certaines femmes demeurent sous-représentées dans ce domaine d’étude. Parmi les femmes souvent absentes de la recherche relative à la fécondité figurent celles qui sont déjà les plus vulnérables aux disparités sanitaires, notamment les travailleuses du sexe, les lesbiennes, homosexuelles, bisexuelles et transsexuelles, les femmes vivant avec le VIH et les consommatrices de drogues. Pourtant, il est important de caractériser les besoins de ces femmes, compte tenu de leurs préoccupations particulières de fécondité, y compris des risques et des obstacles aux soins émanant de la stigmatisation sociale et la discrimination. Cette synthèse passe en revue les données relatives à la fécondité, dégageant les domaines où il existe des lacunes claires de la recherche chez les femmes marginalisées et les conséquences potentielles de ces déficits de données. Dans l’ensemble, à ce jour, la recherche chez les femmes marginalisées a abordé la prévention des grossesses et, dans certains cas, les intentions en matière de fécondité, mais la majorité des études se sont concentrées sur la sécurité de la grossesse après la conception et le bien-être de l’enfant. Néanmoins, précisément parmi les travailleuses du sexe, les données sur la sécurité de la grossesse et le bien-être de l’enfant font largement défaut. Dans chaque groupe marginalisé, les soins avant la conception et l’efficacité des méthodes de conception sont régulièrement sous-étudiés. En fin de compte, l’absence de données épidémiologiques, cliniques et programmatiques limite la disponibilité et la qualité des services de santé génésique pour toutes les femmes et empêche l’action sociale de combler ces lacunes.

Resumen

Las investigaciones relacionadas con la fertilidad comprenden intenciones en cuanto a la fertilidad, atención preconcepción, investigaciones entre mujeres embarazadas y resultados posparto de madres e hijos. Sin embargo, algunas mujeres continúan siendo subrepresentadas en esta área de estudio. Entre las mujeres frecuentemente ausentes de las investigaciones relacionadas con la fertilidad figuran aquéllas que ya son las más vulnerables a disparidades en salud, incluidas las trabajadoras sexuales, lesbianas, gays, bisexuales y mujeres transgénero, mujeres que viven con VIH, y mujeres que consumen drogas. No obstante, la caracterización de las necesidades de estas mujeres es importante, debido a sus inquietudes únicas relacionadas con la fertilidad, tales como riesgos y barreras para obtener servicios, que surgen de estigmas sociales y discriminación. Esta síntesis ofrece una visión general de la evidencia relacionada con la fertilidad, y destaca las brechas en la investigación entre mujeres marginadas y las posibles implicaciones de las insuficiencias de estos datos. En general, las investigaciones realizadas hasta la fecha entre mujeres marginadas han abordado la prevención del embarazo y, en algunos casos, intenciones relacionadas con la fertilidad, pero la mayoría de los estudios se han enfocado en la seguridad del embarazo posconcepción y en el bienestar del niño. Sin embargo, entre trabajadoras sexuales en particular, casi no hay datos disponibles sobre la seguridad del embarazo y el bienestar del niño. En cada grupo marginado, la atención preconcepción y la eficacia de los métodos de concepción continúan siendo poco estudiadas. La ausencia de evidencias epidemiológicas, clínicas y programáticas limita la disponibilidad y calidad de los servicios de salud reproductiva para todas las mujeres, e impide la acción social para abordar estas brechas.

Key Words:

• fertility
• HIV
• female sex workers
• LGBT
• people who use drugs

Introduction

Reproductive health and rights are affirmed through guidelines and programmes that are evidence-based and promote informed choices for all women. These informed choices necessitate research to guide understanding of treatment and care options, risks, benefits, potential outcomes, and costs involved. Broadly, pregnant women have long been known to be under-represented in clinical research, generally due to concerns about the safety of interventions or drugs during pregnancy. Under-representation has resulted in limited evidence for how to treat many chronic and infectious conditions among pregnant women.¹ Consequently, the Office of Research on Women’s Health within the National Institutes of Health in the United States has concluded that there is a clear need for responsible research in pregnant women to address these gaps.²

Moreover, some women are particularly underrepresented within fertility-related research, due to their occupation, health status, behaviours, or sexual and gender identity.³ Specifically, women often forgotten in fertility-related investigations include female sex workers, women living with or affected by HIV, women who use drugs, and lesbian, gay, bisexual and transgender (LGBT) women (Figure 1).^* These underrepresented women are also those who tend to be most vulnerable or have already been pushed to the margins of society. Furthermore, the identified strata of marginalized women are not mutually exclusive and many women, such as female sex workers who are living with HIV, may experience compounded vulnerabilities. Reasons for non-inclusion of certain women in research may be explicit and intentional – due to logistics or safety-related concerns, or due to limited awareness of the need to identify and include specific subsets of women in studies. However, the forces pushing some women to the margins of this research also include social determinants such as discrimination and stigma – including HIV-related stigma, homophobia and transphobia – and lack of power due to economic or gender-related inequalities which collectively undermine the reproductive rights of those not conforming to social expectations.^4,5

Figure 1 Women on the margins of fertility-related research and evidence^a

Exclusion or non-representation of marginalized women from the fertility-related research agenda may have negative consequences, particularly because pregnancy-related risks and challenges may be different or amplified among certain subsets of women. Prevention of unwanted pregnancy is important for all women who are not imminently hoping to expand their family. However, depending on a woman’s age, relationship status, economic or professional situation, and health status, the impact of an unintended pregnancy on the health or well-being of mother or child may vary significantly.⁶ Similarly, many women hoping to conceive may be concerned about their health and safety during pregnancy. For women living with HIV, female sex workers and women who use drugs, reducing the exposure to HIV, sexually transmitted infections (STIs), and drug use during pregnancy and the post-partum period are critical considerations specific to the health and well-being of women and their families. For these women and LGBT women hoping to conceive, knowledge and empowerment about effective, affordable methods to assist safer conception is essential. Furthermore, socially marginalized women generally experience greater health disparities, resulting in reduced access and uptake of healthcare services in general,⁷ and potentially negative pregnancy-related outcomes if engagement in care remains insufficient in the perinatal period.⁸

Optimization of reproductive healthcare for all women is important and understanding the specific needs of women most vulnerable to adverse fertility-related outcomes essential. The objective of this paper is to explore where evidence for marginalized women is lacking in order to provide an overview for a future research agenda.

Methods

To analyse gaps within fertility-related research among socially marginalized women, we developed a framework through which to consider the breadth of fertility-related evidence needs, including: fertility intentions – both fertility desires, and contraceptive use among women not desiring a pregnancy, pregnancy planning and preconception care among women trying to conceive, studies with pregnant women, evaluation of post-partum outcomes, and long-term pregnancy-related effects. Figure 2 illustrates this analytic framework and provides examples of sub-areas that may be evaluated within the biomedical or social science fields at each of the five phases of the fertility continuum. The phases outlined in this framework are used to examine knowledge gaps within each subset of marginalized women described above (Figure 1), highlighting specific questions which remain under-researched or unanswered.

Figure 2 Overview of fertility-related research areas for women of reproductive age.

Using this continuum framework we reviewed the literature to map out the existing state of the evidence and to identify gaps. Given the breadth of the topics covered and the purpose of this exercise to characterize where data is sparse, we conducted a scoping review which sets the groundwork for future more in-depth and focused systematic reviews. The scoping review allowed us to further refine sub-themes within the fertility-related research continuum outlined in Figure 2. Similar to methods used in other scoping reviews, the quality and number of studies reviewed was not quantified, but rather the review was used to map the relevant fertility-related sub-themes and general evidence available within these themes among marginalized populations.⁹ Thus this review is not intended to be an exhaustive presentation of the literature found, but rather a rapid assessment of available evidence from which gaps in the research landscape emerged. We used Medical Subject Headings (MeSH) terms and associated keywords and wildcard terms in Medline/PubMed, Google Scholar and the Google search engine to search literature published through March 31, 2015. MeSH terms included key reproductive health words and the population of interest (e.g. “antenatal care” and “female sex worker”, “contraception” and “people who use drugs”). Multiple iterations of these searches were used to capture the breadth of terms that may be used (e.g. “prenatal care”, “family planning”, “women who sell sex”,” injection drug users”, etc.). Snowball methods and iterative searches using key references from reviewed articles were also used to ascertain additional articles within each sub-group. A summary of the findings and implications are detailed below.

Results

Women living with or affected by HIV

Women living with HIV and affected by HIV have different fertility-related needs. Women living with HIV have participated in an abundance of fertility-related research. The historical focus of fertility-related studies has generally been on the incidence of pregnancy and outcomes of the child, with the preponderance of evidence related to the prevention of HIV mother-to-child transmission (PMTCT). These investigations have been at the foreground of successful global HIV prevention efforts. However, women living with HIV or in relationships affected by HIV have other fertility-related needs as well, including conception planning, safe pregnancy aside from PMTCT, and post-partum care. Important gaps in pregnancy research for women living with HIV, including the need for evidence-based interventions to reduce morbidity due to malaria, tuberculosis and other co-infections among HIV positive pregnant women, have been well detailed previously.¹⁰

There has been substantial evidence assessing contraceptive use and unmet family planning needs of women living with HIV,¹¹ including the impact of antiretrovirals on the efficacy of hormonal contraceptives.¹² Yet, gaps exist in the understanding of knowledge and use of emergency contraception among women living with HIV, as well as to what extent certain antiretroviral drugs may reduce the efficacy of emergency contraception.^13,14 Recently, much attention has been given to the impact of hormonal contraception on HIV disease progression and HIV transmission and acquisition, though evidence of the impact on transmission and acquisition remains inconclusive.^15–19 There have been many calls for integrated family planning and HIV programming efforts; however, evidence of effective integration models have lagged behind and are only slowly emerging.^20,21 The legal status of abortion in many countries and pervasive stigma have also resulted in less information on the relationship between HIV and abortion, including the safety of abortion in the context of HIV and access to post-abortion care.^22–25 Information available suggests that many factors aside from HIV influence decisions to terminate pregnancy, and that abortion is less common among women living with HIV in the antiretroviral era.^3,26 Further knowledge regarding post-abortion care and approaches to effectively integrate HIV and post-abortion care services should be expanded.^27,28 Additionally, evidence has emerged around coerced abortions and forced sterilization of women living with HIV.^3,13 This is alarming and often linked to abortion, as women have reported being coerced to sterilize in order to receive the abortion they are seeking.^3,29 This is an area for which continued attention is required to advocate for the reproductive rights of all women.

Data have emerged in recent years documenting high fertility intentions among women and couples affected by HIV.^30,31 Historically, fertility-related HIV programming has focused on prevention of unintended pregnancy and PMTCT care for women once they are pregnant, with less attention given to the HIV prevention needs of women living with HIV or affected by HIV who are trying to conceive.³² With a limited number of studies, service delivery records related to preconception care, specifically data characterizing safer conception services aiming to minimize the risk of sexual or vertical HIV transmission for HIV-affected couples trying to become pregnant, are scarce.³³ Guidelines for safer conception – relevant to both women living with HIV and women affected by HIV through their partner’s HIV status–are available in several high-income countries as well as in South Africa,^34–38 and are under development by the World Health Organization. However, safer conception implementation has been largely limited to high income settings where resources and infrastructure facilitate options including sperm-washing, intrauterine insemination (IUI), in-vitro fertilization (IVF),^39–41 and/or close monitoring of natural conception while using antiretrovirals.^42,43 Evidence from resource-limited settings has focused on the need for safer conception services, with efficacy and effectiveness verification of these interventions largely outstanding.⁴⁴ Although work is beginning to emerge in this area, key gaps include evaluation of the safety and efficacy of low-cost safer conception methods for HIV prevention, adherence to conception methods, time-to-pregnancy across methods, infertility figures, and comparative effectiveness of safer conception approaches including timed unprotected sex limited to peri-ovulatory periods, manual self-insemination, and unrestricted condomless sex while using antiretrovirals.^45,46 Several implementation questions also remain unanswered related to the optimal delivery of safer conception programmes, such as scale-up feasibility, costs, service utilization, fidelity and impact. Furthermore, for HIV negative women trying to conceive with HIV positive male partners, or other women at high-risk for HIV acquisition, guidance is urgently needed on the safety of vaginal and oral pre-exposure prophylaxis (PrEP) when trying to conceive, during pregnancy and throughout breastfeeding, as condom negotiation may not always be possible within certain relationships. Findings from pregnancy outcomes among women conceiving on PrEP and/or microbicides during trials have provided little reason for concern; however, in all these trials study drug has been stopped once pregnancy was detected.^47–53 Overall, these evidence gaps reflect the only recently expanded HIV prevention options for HIV-affected couples, but also reflect years of stigma, discrimination and lack of legal protection for the reproductive rights of HIV-affected couples.

Among women living with HIV, there has been an increased focus on pregnancy and post-partum periods. Nevertheless, pregnant women remain under-represented within general HIV prevention, treatment, and care studies.⁵⁴ Furthermore, as efforts to eliminate vertical HIV transmission expand, including growing access to lifelong antiretroviral therapy for pregnant women independent of CD4 staging to optimize their own health outcomes as well as the child’s, building the evidence base of effective interventions to reduce loss to follow-up among post-partum women and infants is needed.⁵⁵ Infant and child survival depend on the long-term health outcomes of mothers, and human rights-affirming approaches to support the health of mothers living with HIV will also optimize family health outcomes. Breastfeeding remains an important area for investigation, particularly as the impact of antiretroviral drug exposure to infants is evaluated, as well as the impact of breastfeeding on the health of the mother and her retention in HIV care. While the focus of this review is on women, the long-term impact of in-utero HIV exposure on the extended health outcomes and epigenetics of HIV-exposed, uninfected children is also warranted.^2,56 Recent data from the PROMISE study are a reminder of the continued importance of careful monitoring of the effects of antiretrovirals on morbidity and mortality of antiretroviral exposed infants as well, particularly as new drugs and classes of drugs come to market.⁵⁷

Female sex workers

As occupation generally defines the social perceptions of female sex workers, the fertility-related needs of women engaged in sex work often remain invisible. Studies assessing reproductive histories of female sex workers suggest that the majority of sex workers have children and the relationship between fertility and sex work may be complex.^58–60 The need to provide for children may push some women into sex work, while other women may plan to conceive as an attempt to solidify a partnership and/or leave sex work.^61,62 Women may also desire children for a multitude of reasons independent of their occupation as sex workers.⁶¹ Furthermore, among women not desiring pregnancy, sex work is an occupational risk for unintended pregnancy.⁶³

Despite limited recognition that sex workers are often mothers, health risks associated with sex work make fertility-related research within this population important. Sex workers are often perceived as dangerous women, when they are in fact women in danger. These risks include violence perpetrated against sex workers, high HIV prevalence and sustained antenatal exposure to HIV and other STIs, and limited engagement in healthcare services, which may collectively have deleterious effects on pregnancy outcomes.^64–68 Yet, fertility-related evidence has focused predominantly on the incidence of pregnancy among sex workers and their unmet contraceptive needs.^69–71 Continued efforts to integrate emergency contraception into sex worker-friendly services, and measurement of the impact of these services on unsafe abortions would help to expand the evidence base.⁷²

Even with calls for better integration of sexual and reproductive health care services into HIV prevention programmes for female sex workers, limited implementation results are available exploring the uptake and impact of attempts to promote integration.^73–75 Furthermore, programming efforts and research have focused almost entirely on pregnancy prevention. Recent studies from Canada and two countries in Sub-Saharan Africa have documented that female sex workers, like many other women, desire children.^60,76 However, their reproductive health needs are complicated by divergent reproductive goals with different sexual partners during the same time period. Specifically, pregnancy intentions may be low with certain clients, but high with non-commercial partners, resulting in reliance on barrier contraceptive methods with clients over potentially more effective non-barrier contraceptive methods.⁷⁷ Moreover, despite a high burden and occupational risk for HIV and STIs, stigma and low recognition of the reproductive rights of sex workers limits preconception care and counselling for female sex workers around safer conception and pregnancy within programming efforts.

While high rates of pregnancy incidence among female sex workers have been documented, much less is known about the outcomes of those pregnancies and engagement in care.^63,78,79 Abortion is common among sex workers, though less is known about the safety of abortions or access to post-abortion care.^70,80–82 Existing information suggests that many abortions are unsafe and complications common.^83–85 Legal barriers and criminalization of abortion and sex work in many settings discourage safe abortions and preventive measures, magnifying risk and decreasing access and/or engagement in appropriate care.²⁵ Efforts to expand access to and uptake of post-abortion care and integrated family planning programmes for sex workers are needed, including evidence of whether uptake of post-abortion care and contraception increases if services are specially offered for women engaged in sex work.⁸⁶ Preliminary findings have recently emerged characterizing the engagement of female sex workers in antenatal care in India and Côte d’Ivoire.^83,87 Building on these studies, future studies should characterize condom use, substance use, interactions with clients and duration of sex work during pregnancy. Furthermore, there is dearth of knowledge about practices during the post-partum period, including infant feeding and HIV testing practices, return to sex work, childcare, post-partum depression and contraceptive use. Finally, there is virtually no evidence of child outcomes including HIV mother-to-child transmission, general health and development among children of sex workers.⁸⁸

Lesbian, gay, bisexual and transgender women

Limited consideration has been given to the fertility-related needs of lesbian, gay, bisexual and transgender (LGBT) women. LGBT women desiring to have a child face a variety of decisions about family formation. For lesbian, gay and bisexual women, these include the decision to attempt conception or pursue adoption, questions over where to obtain and who to utilize for donor sperm should conception be attempted (including use of known donors, anonymous donors, or unknown donors willing to be identified at a later stage), determination of which parent will be the gestational carrier, decisions regarding the best conception method for their situation, selection of supportive healthcare providers, and how to navigate legal rights for the family.^89–92 As the majority of lesbians and bisexual women in same-sex relationships share one reproductive challenge, the absence of sperm within their partnership, fertility assistance is often required and lesbians are typically directed down an immediate path of costly infertility services.⁹³ Laws and efforts to protect access to fertility-related services among same-sex couples are only slowly emerging in high income countries and remain outside of the conversation in nearly all resource limited settings,^94,95 and further efforts are needed to ensure access to services and parenthood rights for all individuals are recognized.

Available data from the US Census and the National Survey of Family Growth suggest that the majority of lesbian women desire children and many intend on having a child in the future, though financial challenges associated with conception, social norms and levels of exposure to other LGBT families impact these intentions.^96–98 Existing representative population level data are limited by the heteronormative nature of common survey questions regarding marriage, cohabitation and parenthood which impede interpretation of results.⁹⁹ Other studies designed to assess sociological aspects of fertility desires among lesbian, gay and bisexual same-sex families have been limited by small, non-representative samples.¹⁰⁰ Furthermore, though infrequently considered, many lesbian or bisexual women have had a prior pregnancy with a man, and have high lifetime reports of abortion.^101–103 Young lesbian, gay and bisexual women may engage in riskier sex with men due to confusion about their sexuality and attention to the mental health, substance use and pregnancy risks in this group is warranted.¹⁰⁴ Clinicians and researchers should also consider prior abortion history when caring for fertility-related needs of these women.

In terms of preconception care and assisted reproduction, lesbian couples comprise a growing percentage of clients within fertility centres.⁹⁴ Though many private fertility clinics report treating heterosexual and same-sex couples, globally there is limited understanding of the proportion of services which accept LGBT women into their practice and non-response biases within existing studies limit interpretation.¹⁰⁵ Limited data available suggest that lesbian women accessing fertility and maternity services in high income countries tend to have positive experiences with healthcare providers, yet heterosexism within the fertility system has commonly been noted.^106–110 Additional insights about experiences within fertility centres, factors influencing conception-related decisions, and preferences for care are needed.

Research on pregnancy incidence and outcomes, including time-to-conception, number of attempts prior to conception, subfertility, pregnancy loss, and cost of conception is very limited among lesbian women. Studies from the UK and Swedish fertility clinics suggest that lesbian women conceive at rates similar to heterosexual women using donor sperm and IUI or IVF.^111,112 Comparisons of these methods with home-based insemination utilizing donor sperm have not been published. Additional evaluation assessing outcomes and comparative effectiveness of the various approaches for lesbian couples (home-based vaginal insemination, clinic-based intracervical insemination, IUI and IVF) factoring in both costs and time-to-conception are required to help couples make informed decisions about their conception options. Lessons learned from heterosexual couples are not sufficient as those couples are seeking care due to infertility challenges which are often not relevant for same-sex couples.

The preponderance of post-partum evidence available focuses on the well-being of children with same-sex versus heterosexual parents, emphasizing similar health and well-being outcomes for children across family types,^113–116 while the effect of anonymous versus identifiable sperm donors on health outcomes of children, as well as relationships between donor siblings, are not well understood.^117–120 Among lesbian couples, there is emerging data on post-partum depression, highlighting the potential for elevated post-partum depression risk and the importance of social support, as families and legal structures may accentuate inequalities in these families.^121–123 In the coming years assessments of long-term family outcomes for same-sex families remain important, but evidence to date suggests that children of same-sex couples have similar psychosocial development outcomes as children from heterosexual parents, though awareness of stigma, discrimination and homophobia must be managed for children of same-sex couples.¹¹³ Future attention should be given to bonding and mental health outcomes of gestational versus non-gestational mothers, particularly in contexts in which the legal rights of non-gestational mothers are not equally protected.

Fertility issues differ among transgender women and lesbian or bisexual women with transgender women for partners, due to different potential conception options based on the transgender partners’ reproductive biology. However, the fertility-related needs within transgender women are no less complex as considerations of prior clinical procedures and sperm preservation are relevant and stigma facing reproduction within this population is substantial.¹²⁴ Furthermore, though transgender men do not fall within the classification of LGBT women, depending on their clinical history they may be able to become pregnant or donate oocytes to their relationship, contributing further to the complexity around these issues. An understanding of the fertility desires and intentions among transgender individuals remains an area for further growth. The extent to which fertility centres support sperm preservation and oocyte preservation for transgender individuals is unknown as reproductive options are infrequently considered for the transgender community.¹²⁵ Evidence of care experiences from transgender individuals are even more limited, though reports from transgender men biologically capable of conceiving indicate that preconception periods are associated with distress, discrimination within the healthcare system and limited available medical evidence to guide decisions.^126,127 Pregnancy incidence and outcomes data within this population are non-existent.

Women who use drugs

Trends in drug use during pregnancy in North America have remained relatively steady over time with changes primarily in specific drug use patterns.^128,129 Data outlining trends from outside of North America are scarce. Substance use in women increases risk of unintended pregnancy due to lower condom use during sex while using drugs and lower perceived risk of conceiving among women with drug-related amenorrhea.¹³⁰ The use of certain illicit drugs during and following pregnancy has been shown to have serious adverse health consequences for the child. Consequently, early engagement and identification of drug use during pregnancy is important to provide support to the mother in risk reduction approaches.¹³¹ Recommendations for treatment and research needs of pregnant women who use drugs have been recently proposed by the World Health Organization (WHO).¹³² However, as noted by the WHO and others, stigma and discrimination towards pregnant women who use drugs continues to delay engagement in antenatal care or other treatment programmes and research should also address these challenges.¹³³

The majority of fertility-related evidence among women who use drugs focuses on women after they present to antenatal or delivery care, emphasizing the short- and long-term effects of foetal drug exposure, as well as the effects of buprenorphine and harm reduction methadone maintenance therapies.^134–136 Low contraceptive use and high unmet need for family planning has been documented in several studies.^63,137–139 Further investigation is needed, particularly into how sexual and reproductive health services and parenting skills-building can be integrated into substance use treatment programmes and other health interventions serving people who use drugs.^140–142 High rates of abortion have been reported among women who use drugs, some of whom are also sex workers, however, reduction in abortion-related risks and integration of family planning and post-abortion care in this population has not adequately been documented.^143–145 Fertility-related assessments prior to pregnancy in this population are limited, although studies focused on women living with HIV in Canada, including women who use drugs, suggested that drug use did not affect fertility intentions.¹⁴⁶ Evidence-based and human rights-affirming interventions are needed at this time when certain programming efforts incentivize contraceptive use or sterilization among women who use drugs.^147,148

Finally, better understanding of the barriers to engagement in ante and perinatal care among women who use drugs, and of facilitators to earlier access of services, would improve how health risks are addressed during pregnancy. Available evidence consistently suggest that women who use drugs access antenatal care later than other pregnant women and that intimate partner violence may further exacerbate drug use during pregnancy.^149,150 Late or inadequate engagement in care can also lead to other adverse outcomes among pregnant women who use drugs, such as reported associations between drug use and heightened rates of mother-to-child transmission of HIV and hepatitis C.^151–153 Little is known about post-partum engagement in care among mothers who use drugs. Furthermore, few longitudinal studies consider long-term outcomes of mother-child dyads with a history of substance use.¹⁵⁴

Conclusions

While each group of women assessed has a distinctive set of circumstances, certain themes emerged when comparing the literature available across groups (Table 1). Specifically, the focus of fertility-related research among marginalized women has historically been limited to pregnancy incidence and health outcomes of infants and children and to the prevention of unintended pregnancy. These are unarguably critical areas for which investigation is essential to inform the implementation of programmes promoting the health and well-being of women and children. However, work focused on promoting reproductive choices, including safer pregnancy options for women desiring children, has been far more limited. In part, this omission may reflect that efforts to support desired conception among marginalized women are less valued than programmes preventing their unintended pregnancies. Additionally, despite findings and advocacy in support of integration of sexual and reproductive health care into existing services for women living with HIV, sex workers, and women who use drugs – such as HIV treatment or prevention programmes, mobile outreach initiatives, and substance use treatments programmes – limited implementation and social science studies have been published characterizing the effectiveness of these services, barriers to engagement in care and pathways to address stigma and discrimination. Long-term pregnancy-related outcomes of mothers and children are necessary to better understand health needs and impact over time, but remain key gaps in fertility-related research among marginalized women. Overcoming socioeconomic and structural barriers with multicomponent interventions will be required to achieve optimal health outcomes for marginalized women and their children. Furthermore, attention to reproductive options for marginalized women, as well as non-HIV related child outcomes, have largely been concentrated in high-income countries to date and greater understanding of the fertility-related continuum for marginalized women is called for in low- and middle-income countries.

Table 1 Summary of Research Gaps among Marginalized Women of Reproductive Age.

	Key research gaps
Women living with or affected by HIV	• Conclusive evidence of the impact of hormonal contraception on HIV transmission and acquisition • Effective integration models for HIV and family planning • Evaluation of safer conception approaches in resource limited settings, including safety and efficacy of approaches, adherence to methods, time-to-pregnancy, comparative effectiveness of approaches and feasibility and optimal models for scale-up. • Infertility or sub-fertility in the context of HIV • Impact of lifelong maternal antiretroviral initiation during pregnancy on long-term maternal and child outcomes
Female sex workers	• Demonstration of the impact of integration of reproductive health programming into HIV prevention and care programmes for female sex workers • Additional understanding of fertility intentions, services needed to ensure safer pregnancy • Information around sex work and pregnancy, post-partum breastfeeding, depression and return to sex work • HIV mother-to-child transmission rates in the context of frequent sexually transmitted co-infections and structural barriers to ART care and adherence
LGBT women	• Additional examination of fertility intentions and experiences attempting conception among lesbians, gay and bisexual women and couples • Social science and programming evidence on fertility-related needs and services for transgender women • Comparative effectiveness of conception approaches for lesbian/gay/bisexual women with no known fertility issues which account for costs and time-to-conception across methods • Donor anonymity and health outcomes of children • Short and long-term post-partum depression and mental health outcomes of gestational and non-gestational LGBT mothers
Women who use drugs	• Fertility intentions of women who use drugs • Models for integration of family planning and reproductive health care into harm reduction programmes for women who use drugs • Barriers and facilitators to engagement in antenatal and postnatal care • Long-term maternal and infant outcomes (cohorts) of women who used drugs during or after pregnancy • More research in income limited settings

Despite the described research gaps, extensive evidence of fertility-related needs among marginalized women is also available. Through considering both the evidence and the gaps, interventions can be designed and better health outcomes can potentially be achieved. The need for rigorous assessment of the effectiveness of interventions in particular is crucial. Ideally, services would be scaled up and available for all women immediately. However, given legal barriers, the funding climate and competing demands, programming is unlikely to be scaled-up in the absence of clear evidence of potential impact. Thus careful design and assessment of potential interventions which maximize understanding of the true value of interventions – particularly among those most vulnerable to poor health outcomes – are needed to ensure that resources are effectively reaching those for whom the impact may be greatest. Furthermore it will be important to quantify the size of the denominator for which unmet need remains (i.e. what are the population sizes of these marginalized women and how many remain unreached?). The cumulative effect of knowledge gaps is insufficient programming efforts and resource allocation for these critical areas, and an absence of social action to address unquantified health needs or scale-up interventions for which evidence is not available.

Limitations to this review must be acknowledged. There are many women at the margins, including women living in extreme poverty, refugees, migrants, and others who are not explicitly represented here. We have focused on fertility-related gaps among those marginalized due to social stigmas, such as occupation, health status, gender identity or behaviour, however, we do not endorse the omission of other marginalized women from the research agenda. Furthermore, the breadth of topics covered in this review limit the depth to which we can present each of the fertility-related areas. Whenever possible we have included references to thorough reviews conducted within sub-areas of this review. Rather than a stopping point, this analysis should be viewed as a way of considering further areas in need of exploration, intervention and scientific growth and expansion. Finally, though vulnerable to negative health outcomes, it should be noted that these women on the margins have different rights, services and challenges in different settings. Their rights are increasingly being recognized because they have demanded to be acknowledged and included in the conversation about their health, and effective research must reflect the voices and priorities of these women and involve true partnerships between researchers and communities.

The potential impact of excluding marginalized women from the comprehensive fertility-related research agenda is that evidence and programmes for their specific health needs are unavailable. Notably, the absence of fertility-related evidence among marginalized women limits the possibility to inform clinical practice or programmes intending to optimize health outcomes for all pregnant women. These women for whom guidance is missing are often amongst the most vulnerable or least served within their communities, frequently experiencing health inequities, stigma and discrimination. A more inclusive fertility-related research agenda is warranted to fill these gaps in order to enhance the reproductive health and rights of all women.

Notes

* Note that we include gay women in addition to lesbians and bisexual women, as identities within the community vary. It should be noted that many other women who have sex with women may have other identities outside of ‘LGBT women’ (e.g., gender variant, gender queer, etc.) for which these research gaps may also be relevant.