A critical systematic review and meta-analyses of risk factors for fertility problems in a globalized world.

Globally, fertility awareness efforts include well-established risk factors for fertility problems. Risks disproportionately affecting women in the Global South, however, are neglected. To address this gap, we conducted a systematic review and meta-analyses of relevant risk factors to examine the association between risk factors and fertility problems. MEDLINE, Embase, Cochrane Library, regional databases and key organizational websites were used. Three authors screened and extracted data independently. Studies assessing exposure to risk (clinical, community-based samples) were included, and studies without control groups were excluded. Outcome of interest was fertility problems, e.g. inability to achieve pregnancy, live birth, neonatal death depending on study. The Newcastle-Ottawa Scale was used to assess study quality. A total of 3843 studies were identified, and 62 were included (58 in meta-analyses; n = 111,977). Results revealed the following: a ninefold risk of inability to become pregnant in genital tuberculosis (OR 8.91, 95% CI 1.89 to 42.12); an almost threefold risk in human immunodeficiency virus (OR 2.93, 95% CI 1.95 to 4.42) and bacterial vaginosis (OR 2.81, 95% CI 1.85 to 4.27); a twofold risk of tubal-factor infertility in female genital mutilation/cutting-Type II/III (OR 2.06, 95% CI 1.03 to 4.15); and postnatal mortality in consanguinity (stillbirth, OR 1.28, 95% CI 1.04 to 1.57; neonatal death, OR 1.57, 95% CI 1.22 to 2.02). It seems that risk factors affected reproductive processes through multiple pathways. Health promotion encompassing relevant health indicators could enhance prevention and early detection of fertility problems in the Global South and disproportionately affected populations. The multifactorial risk profile reinforces the need to place fertility within global health initiatives.

Empathetic application of machine learning may address appropriate utilization of ART.

The value of artificial intelligence to benefit infertile patients is a subject of debate. This paper presents the experience of one aspect of artificial intelligence, machine learning, coupled with patient empathy to improve utilization of assisted reproductive technology (ART), which is an important aspect of care that is under-recognized. Although ART provides very effective options for infertile patients to build families, patients often discontinue ART when further treatment is likely to be beneficial and most of these patients do not achieve pregnancy without medical aid. Use of ART is only in part dependent on financial considerations; stress and other factors play a major role, as shown by high discontinuation rates despite reimbursement. This commentary discusses challenges and strategies to providing personalized ART prognostics based on machine learning, and presents a case study where appropriate use of such prognostics in ART centres is associated with a trend towards increased ART utilization.

The International Glossary on Infertility and Fertility Care, 2017.

STUDY QUESTION: Can a consensus and evidence-driven set of terms and definitions be generated to be used globally in order to ensure consistency when reporting on infertility issues and fertility care interventions, as well as to harmonize communication among the medical and scientific communities, policy-makers, and lay public including individuals and couples experiencing fertility problems? SUMMARY ANSWER: A set of 283 consensus-based and evidence-driven terminologies used in infertility and fertility care has been generated through an inclusive consensus-based process with multiple stakeholders. WHAT IS KNOWN ALREADY: In 2006 the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) published a first glossary of 53 terms and definitions. In 2009 ICMART together with WHO published a revised version expanded to 87 terms, which defined infertility as a disease of the reproductive system, and increased standardization of fertility treatment terminology. Since 2009, limitations were identified in several areas and enhancements were suggested for the glossary, especially concerning male factor, demography, epidemiology and public health issues. STUDY DESIGN, SIZE, DURATION: Twenty-five professionals, from all parts of the world and representing their expertise in a variety of sub-specialties, were organized into five working groups: clinical definitions; outcome measurements; embryology laboratory; clinical and laboratory andrology; and epidemiology and public health. Assessment for revisions, as well as expansion on topics not covered by the previous glossary, were undertaken. A larger group of independent experts and representatives from collaborating organizations further discussed and assisted in refining all terms and definitions. PARTICIPANTS/MATERIALS, SETTING, METHODS: Members of the working groups and glossary co-ordinators interacted through electronic mail and face-to-face in international/regional conferences. Two formal meetings were held in Geneva, Switzerland, with a final consensus meeting including independent experts as well as observers and representatives of international/regional scientific and patient organizations. MAIN RESULTS AND THE ROLE OF CHANCE: A consensus-based and evidence-driven set of 283 terminologies used in infertility and fertility care was generated to harmonize communication among health professionals and scientists as well as the lay public, patients and policy makers. Definitions such as 'fertility care' and 'fertility awareness' together with terminologies used in embryology and andrology have been introduced in the glossary for the first time. Furthermore, the definition of 'infertility' has been expanded in order to cover a wider spectrum of conditions affecting the capacity of individuals and couples to reproduce. The definition of infertility remains as a disease characterized by the failure to establish a clinical pregnancy; however, it also acknowledges that the failure to become pregnant does not always result from a disease, and therefore introduces the concept of an impairment of function which can lead to a disability. Additionally, subfertility is now redundant, being replaced by the term infertility so as to standardize the definition and avoid confusion. LIMITATIONS, REASONS FOR CAUTION: All stakeholders agreed to the vast majority of terminologies included in this glossary. In cases where disagreements were not resolved, the final decision was reached after a vote, defined before the meeting as consensus if passed with 75%. Over the following months, an external expert group, which included representatives from non-governmental organizations, reviewed and provided final feedback on the glossary. WIDER IMPLICATIONS OF THE FINDINGS: Some terminologies have different definitions, depending on the area of medicine, for example demographic or clinical as well as geographic differences. These differences were taken into account and this glossary represents a multinational effort to harmonize terminologies that should be used worldwide. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: N/A.

Management of ovarian stimulation for IVF: narrative review of evidence provided for World Health Organization guidance.

In this paper, a review of evidence provided to the World Health Organization (WHO) guideline development, who prepare global guidance on the management of ovarian stimulation for women undergoing IVF, is presented. The purpose of ovarian stimulation is to facilitate retrieval of multiple oocytes during a single IVF cycle. Availability of multiple oocytes compensates for inefficiencies in subsequent stages of the cycle, which include oocyte maturation, IVF, embryo culture, embryo transfer, and implantation. Multiple embryos can be transferred in most women, and spare embryos can be frozen to allow for future chances of pregnancy without the need for repeated ovarian stimulation and oocyte retrieval. Our evidence synthesis team addressed 10 clinical questions on management of ovarian stimulation for IVF, prepared a narrative review of the evidence and drafted recommendations to be considered through WHO guideline development processes. Our main outcome measures were live birth, clinical pregnancy, and ovarian hyperstimulation syndrome.

Blastocyst culture using single versus sequential media in clinical IVF: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: The purpose of this study was to undertake a review of the available evidence comparing the use of a single medium versus sequential media for embryo culture to the blastocyst stage in clinical IVF. METHODS: We searched the Cochrane Central, PubMed, Scopus, ClinicalTrials.gov, Current Controlled Trials and WHO International Clinical Trials Registry Platform to identify randomized controlled trials comparing single versus sequential media for blastocyst culture and ongoing pregnancy rate. Included studies randomized either oocytes/zygotes or women. Eligible oocyte/zygote studies were analyzed to assess the risk difference (RD) and 95 % confidence intervals (CI) between the two media systems; eligible woman-based studies were analyzed to assess the risk ratio (RR) and 95 % CI for clinical pregnancy rate. RESULTS: No differences were observed between single and sequential media for either ongoing pregnancy per randomized woman (relative risk (RR) = 0.9, 95 % CI = 0.7 to 1.3, two studies including 246 women, I 2 = 0 %) or clinical pregnancy per randomized woman (RR = 1.0, 95 % CI = 0.7 to 1.4, one study including 100 women); or miscarriage per clinical pregnancy: RR = 1.3, 95 % CI = 0.4 to 4.3, two studies including 246 participants, I 2 = 0 %). Single media use was associated with an increase blastocyst formation per randomized oocyte/zygote (relative distribution (RD) = +0.06, 95 % CI = +0.01 to +0.12, ten studies including 7455 oocytes/zygotes, I 2 = 83 %) but not top/high blastocyst formation (RD = +0.05, 95 % CI = -0.01 to +0.11, five studies including 3879 oocytes/zygotes, I 2 = 93 %). The overall quality of the evidence was very low for all these four outcomes. CONCLUSIONS: Although using a single medium for extended culture has some practical advantages and blastocyst formation rates appear to be higher, there is insufficient evidence to recommend either sequential or single-step media as being superior for the culture of embryos to days 5/6. Future studies comparing these two media systems in well-designed trials should be performed.

Achieving pregnancy safely: perspectives on timed vaginal insemination among HIV-serodiscordant couples and health-care providers in Kisumu, Kenya.

In female-positive HIV-serodiscordant couples desiring children, home timed vaginal insemination (TVI) of semen during the fertile period along with consistent condom use may reduce the risk of HIV transmission when the man is HIV-uninfected. In sub-Saharan Africa, up to 45% of HIV-infected women desire to have more children. HIV viral load assessment is not routinely available in low-resource countries for monitoring adherence and response to antiretroviral therapy. Therefore, in these settings, timed unprotected intercourse without assurance of HIV viral suppression may pose unnecessary risks. TVI, a simple and affordable intervention, can be considered an adjunct method and option of safer conception for HIV prevention with treatment of the HIV-infected partner and/or pre-exposure prophylaxis. We conducted five mixed and single-sex focus group discussions comprised of 33 HIV-serodiscordant couples and health-care providers in the Nyanza region of Kenya to assess the acceptability and feasibility of TVI as a safer method of conception. The transcribed data were analyzed using a grounded theory approach. We found that educating and counseling HIV-serodiscordant couples on TVI could make it an acceptable and feasible safer conception method when associated with frequent communication and home visits by health-care providers. The findings of this study indicate that implementation studies that integrate training and counseling of HIV-serodiscordant couples and health-care providers on TVI combined with consistent condom use are needed. Acknowledging and supporting the reproductive choice and needs of female positive, male negative HIV-serodiscordant couples who desire children should also include the use of assisted reproductive services at the same time as pharmaceutical options that prevent sexual HIV transmission.

Infertility services integrated within the maternal health department of a public hospital in a low-income country, Rwanda.

Objective: To describe the initiation, integration, and costs of reduced-cost infertility services within the maternal health department of a public hospital in a low-income country. Design: Retrospective review of the clinical and laboratory components of patients undergoing in vitro fertilization (IVF) treatment in Rwanda from 2018 to 2020. Setting: Academic tertiary referral hospital in Rwanda. Patients: Patients seeking infertility services beyond the primary gynecological options. Interventions: The national government furnished facilities and personnel, and the Rwanda Infertility Initiative, an international nongovernmental organization, provided training, equipment, and materials. The incidence of retrieval, fertilization, embryo cleavage, transfer, and conception (observed until ultrasound verification of intrauterine pregnancy with fetal heartbeat) were analyzed. Cost calculations used the government-issued tariff specifying insurers' payments and patients' copayments with projected delivery rates using early literature. Main Outcome Measures: Assessment of functional clinical and laboratory infertility services and costs. Results: A total of 207 IVF cycles were initiated, 60 of which led to transfer of ≥1 high-grade embryo and 5 to ongoing pregnancies. The projected average cost per cycle was 1,521 USD. Using optimistic and conservative assumptions, the estimated costs per delivery for women <35 years were 4,540 and 5,156 USD, respectively. Conclusions: Reduced-cost infertility services were initiated and integrated within a maternal health department of a public hospital in a low-income country. This integration required commitment, collaboration, leadership, and a universal health financing system. Low-income countries, such as Rwanda, might consider infertility treatment and IVF for younger patients as part of an equitable and affordable health care benefit.

Historical walk: the HRP Special Programme and infertility.

BACKGROUND/AIMS: The HRP Special Programme (HRP) began addressing 'reproduction' problems (infertility) at the same time as 'fertility regulation' (contraception). METHODS: This report is based upon data collected from official HRP Scientific and Technical Reports. RESULTS: In the 1970s, HRP supported research on human and nonhuman primate models to address the basic biology of reproduction. Importantly, however, it was the multicountry clinical research studies sponsored by HRP during the 1970s and 1980s which led to the identification of not only the large burden of disease but also global patterns of causation of infertility. The next decade saw the development of WHO guidelines and manuals for diagnosis, management, and treatment of infertile women and men, with HRP-sponsored operations research focused on adaptation within primary health care settings. Consensus consultations held during 2001 through 2011 resulted in recommendations to stakeholders, as well as the identification of barriers and inequities in access to infertility care services. CONCLUSION: With renewed focus on infertility through the current development of revised guidelines and manuals, and the desire to support critical clinical research protocols, including adaptation and implementation research for management and monitoring tools being developed through international partners, HRP will continue to support future success stories in family, maternal, child, and reproductive health.

Should home-based ovulation predictor kits be offered as an additional approach for fertility management for women and couples desiring pregnancy? A systematic review and meta-analysis.

INTRODUCTION: To inform the WHO Guideline on self-care interventions, we conducted a systematic review of the impact of ovulation predictor kits (OPKs) on time-to-pregnancy, pregnancy, live birth, stress/anxiety, social harms/adverse events and values/preferences. METHODS: Included studies had to compare women desiring pregnancy who managed their fertility with and without OPKs, measure an outcome of interest and be published in a peer-reviewed journal. We searched for studies on PubMed, CINAHL, LILACS and EMBASE through November 2018. We assessed risk of bias assessed using the Cochrane tool for randomised controlled trials (RCTs) and the Evidence Project tool for observational studies, and conducted meta-analysis using random effects models to generate pooled estimates of relative risk (RR). RESULTS: Four studies (three RCTs and one observational study) including 1487 participants, all in high-income countries, were included. Quality of evidence was low. Two RCTs found no difference in time-to-pregnancy. All studies reported pregnancy rate, with mixed results: one RCT from the 1990s among couples with unexplained or male-factor infertility found no difference in clinical pregnancy rate (RR: 1.09, 95% CI 0.51 to 2.32); two more recent RCTs found higher self-reported pregnancy rates among OPK users (pooled RR: 1.40, 95% CI 1.08 to 1.80). A small observational study found higher rates of pregnancy with lab testing versus OPKs among women using donor insemination services. One RCT found no increase in stress/anxiety after two menstrual cycles using OPKs, besides a decline in positive affect. No studies measured live birth or social harms/adverse events. Six studies presented end-users' values/preferences, with almost all women reporting feeling satisfied, comfortable and confident using OPKs. CONCLUSION: A small evidence base, from high-income countries and with high risk of bias, suggests that home-based use of OPKs may improve fertility management when attempting to become pregnant with no meaningful increase in stress/anxiety and with high user acceptability. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO registration number CRD42019119402.

Empowering HIV-infected women in low-resource settings: A pilot study evaluating a patient-centered HIV prevention strategy for reproduction in Kisumu, Kenya.

BACKGROUND: Female positive/male negative HIV-serodiscordant couples express a desire for children and may engage in condomless sex to become pregnant. Current guidelines recommend antiretroviral treatment in HIV-serodiscordant couples, yet HIV RNA viral suppression may not be routinely assessed or guaranteed and pre-exposure prophylaxis may not be readily available. Therefore, options for becoming pregnant while limiting HIV transmission should be offered and accessible to HIV-affected couples desiring children. METHODS: A prospective pilot study of female positive/male negative HIV-serodiscordant couples desiring children was conducted to evaluate the acceptability, feasibility, and effectiveness of timed vaginal insemination. Eligible women were 18-34 years with regular menses. Prior to timed vaginal insemination, couples were observed for two months, and tested and treated for sexually transmitted infections. Timed vaginal insemination was performed for up to six menstrual cycles. A fertility evaluation and HIV RNA viral load assessment was offered to couples who did not become pregnant. FINDINGS: Forty female positive/male negative HIV-serodiscordant couples were enrolled; 17 (42.5%) exited prior to timed vaginal insemination. Twenty-three couples (57.5%) were introduced to timed vaginal insemination; eight (34.8%) achieved pregnancy, and six live births resulted without a case of HIV transmission. Seven couples completed a fertility evaluation. Four women had no demonstrable tubal patency bilaterally; one male partner had decreased sperm motility. Five women had unilateral/bilateral tubal patency; and seven women had an HIV RNA viral load (≥ 400 copies/mL). CONCLUSION: Timed vaginal insemination is an acceptable, feasible, and effective method for attempting pregnancy. Given the desire for children and inadequate viral suppression, interventions to support safely becoming pregnant should be integrated into HIV prevention programs.

IUI: review and systematic assessment of the evidence that supports global recommendations.

BACKGROUND: IUI with or without ovarian stimulation (OS) has become a first-line treatment option for many infertile couples, worldwide. The appropriate treatment modality for couples and their clinical management through IUI or IUI/OS cycles must consider maternal and perinatal outcomes, most notably the clinical complication of higher-order multiple pregnancies associated with IUI-OS. With a current global emphasis to continue to decrease maternal and perinatal mortality and morbidity, the World Health Organization (WHO) had established a multi-year project to review the evidence for the establishment of normative guidance for the implementation of IUI as a treatment to address fertility problems, and to consider its cost-effectiveness for lower resource settings. OBJECTIVE AND RATIONALE: The objective of this review is to provide a review of the evidence of 13 prioritized questions that cover IUI with and without OS. We provide summary recommendations for the development of global, evidence-based guidelines based upon methodology established by the WHO. SEARCH METHODS: We performed a comprehensive search using question-specific relevant search terms in May 2015. For each PICO (Population, Intervention, Comparison and Outcomes) drafted by WHO, specific search terms were used to find the available evidence in MEDLINE (1950 to May 2015) and The Cochrane Library (until May 2015). After presentation to an expert panel, a further hand search of references in relevant reviews was performed up to January 2017. Articles that were found to be relevant were read and analysed by two investigators and critically appraised using the Cochrane Collaboration's tool for assessing risk of bias, and AMSTAR in case of systematic reviews. The quality of the evidence was assessed using the GRADE system. An independent expert review process of our analysis was conducted in November 2016. OUTCOMES: This review provides an assessment and synthesis of the evidence that covers 13 clinical questions including the indications for the use of IUI versus expectant management, the sperm parameters required, the best and optimal method of timing and number of inseminations per cycle, prevention strategies to decrease multiple gestational pregnancies, and the cost-effectiveness of IUI versus IVF. We provide an evidence-based formulation of 20 recommendations, as well as two best practice points that address the integration of methods for the prevention of infection in the IUI laboratory. The quality of the evidence ranges from very low to high, with evidence that may be decades old but of high quality, however, we further discuss where critical research gaps in the evidence remain. WIDER IMPLICATIONS: This review presents an evidence synthesis assessment and includes recommendations that will assist health care providers worldwide with their decision-making when considering IUI treatments, with or without OS, for their patients presenting with fertility problems.

The International Glossary on Infertility and Fertility Care, 2017.

STUDY QUESTION: Can a consensus and evidence-driven set of terms and definitions be generated to be used globally in order to ensure consistency when reporting on infertility issues and fertility care interventions, as well as to harmonize communication among the medical and scientific communities, policy-makers, and lay public including individuals and couples experiencing fertility problems? SUMMARY ANSWER: A set of 283 consensus-based and evidence-driven terminologies used in infertility and fertility care has been generated through an inclusive consensus-based process with multiple stakeholders. WHAT IS KNOWN ALREADY: In 2006 the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) published a first glossary of 53 terms and definitions. In 2009 ICMART together with WHO published a revised version expanded to 87 terms, which defined infertility as a disease of the reproductive system, and increased standardization of fertility treatment terminology. Since 2009, limitations were identified in several areas and enhancements were suggested for the glossary, especially concerning male factor, demography, epidemiology and public health issues. STUDY DESIGN, SIZE, DURATION: Twenty-five professionals, from all parts of the world and representing their expertise in a variety of sub-specialties, were organized into five working groups: clinical definitions; outcome measurements; embryology laboratory; clinical and laboratory andrology; and epidemiology and public health. Assessment for revisions, as well as expansion on topics not covered by the previous glossary, were undertaken. A larger group of independent experts and representatives from collaborating organizations further discussed and assisted in refining all terms and definitions. PARTICIPANTS/MATERIALS, SETTING, METHODS: Members of the working groups and glossary co-ordinators interacted through electronic mail and face-to-face in international/regional conferences. Two formal meetings were held in Geneva, Switzerland, with a final consensus meeting including independent experts as well as observers and representatives of international/regional scientific and patient organizations. MAIN RESULTS AND THE ROLE OF CHANCE: A consensus-based and evidence-driven set of 283 terminologies used in infertility and fertility care was generated to harmonize communication among health professionals and scientists as well as the lay public, patients and policy makers. Definitions such as 'fertility care' and 'fertility awareness' together with terminologies used in embryology and andrology have been introduced in the glossary for the first time. Furthermore, the definition of 'infertility' has been expanded in order to cover a wider spectrum of conditions affecting the capacity of individuals and couples to reproduce. The definition of infertility remains as a disease characterized by the failure to establish a clinical pregnancy; however, it also acknowledges that the failure to become pregnant does not always result from a disease, and therefore introduces the concept of an impairment of function which can lead to a disability. Additionally, subfertility is now redundant, being replaced by the term infertility so as to standardize the definition and avoid confusion. LIMITATIONS, REASONS FOR CAUTION: All stakeholders agreed to the vast majority of terminologies included in this glossary. In cases where disagreements were not resolved, the final decision was reached after a vote, defined before the meeting as consensus if passed with 75%. Over the following months, an external expert group, which included representatives from non-governmental organizations, reviewed and provided final feedback on the glossary. WIDER IMPLICATIONS OF THE FINDINGS: Some terminologies have different definitions, depending on the area of medicine, for example demographic or clinical as well as geographic differences. These differences were taken into account and this glossary represents a multinational effort to harmonize terminologies that should be used worldwide. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: N/A.

The diagnosis of male infertility: an analysis of the evidence to support the development of global WHO guidance-challenges and future research opportunities.

BACKGROUND: Herein, we describe the consensus guideline methodology, summarize the evidence-based recommendations we provided to the World Health Organization (WHO) for their consideration in the development of global guidance and present a narrative review of the diagnosis of male infertility as related to the eight prioritized (problem or population (P), intervention (I), comparison (C) and outcome(s) (O) (PICO)) questions. Additionally, we discuss the challenges and research gaps identified during the synthesis of this evidence. OBJECTIVE AND RATIONALE: The aim of this paper is to present an evidence-based approach for the diagnosis of male infertility as related to the eight prioritized PICO questions. SEARCH METHODS: Collating the evidence to support providing recommendations involved a collaborative process as developed by WHO, namely: identification of priority questions and critical outcomes; retrieval of up-to-date evidence and existing guidelines; assessment and synthesis of the evidence; and the formulation of draft recommendations to be used for reaching consensus with a wide range of global stakeholders. For each draft recommendation the quality of the supporting evidence was then graded and assessed for consideration during a WHO consensus. OUTCOMES: Evidence was synthesized and recommendations were drafted to address the diagnosis of male infertility specifically encompassing the following: What is the prevalence of male infertility and what proportion of infertility is attributable to the male? Is it necessary for all infertile men to undergo a thorough evaluation? What is the clinical (ART/non ART) value of traditional semen parameters? What key male lifestyle factors impact on fertility (focusing on obesity, heat and tobacco smoking)? Do supplementary oral antioxidants or herbal therapies significantly influence fertility outcomes for infertile men? What are the evidence-based criteria for genetic screening of infertile men? How does a history of neoplasia and related treatments in the male impact on (his and his partner's) reproductive health and fertility options? And lastly, what is the impact of varicocele on male fertility and does correction of varicocele improve semen parameters and/or fertility? WIDER IMPLICATIONS: This evidence synthesis analysis has been conducted in a manner to be considered for global applicability for the diagnosis of male infertility.

A systematic review and narrative report of the relationship between infertility, subfertility, and intimate partner violence.

BACKGROUND: Infertility/subfertility could be a formerly unrecognized risk factor for intimate partner violence (IPV). OBJECTIVES: To review the evidence on the association between infertility/subfertility in women and the risk of IPV. SEARCH STRATEGY: Seven databases were searched for articles published in English or Spanish between January 2000 and July 2015. SELECTION CRITERIA: Studies were included if they analyzed the relationship between infertility/subfertility and IPV in a quantitative manner. DATA COLLECTION AND ANALYSIS: A systematic search was completed by one author, and articles meeting the inclusion/exclusion criteria were chosen by two authors. It was not possible to pool the data because of heterogeneity in the study design, the methods, and the definitions of IPV and infertility/subfertility found across the studies. Instead, a narrative report was completed. MAIN RESULTS: Twenty-one papers met the inclusion/exclusion criteria. The available evidence indicated that infertility/subfertility is associated with IPV in low- and middle-income countries (LMICs). CONCLUSIONS: Infertility/subfertility is associated with an increased risk of experiencing IPV in LMICs. Future research should focus on studies with a homogenous design, rigorous methodology, and appropriately selected study and control groups. Qualitative research would also be invaluable to assess the impact of relevant social variables on outcomes.

Effectiveness of semen washing to prevent human immunodeficiency virus (HIV) transmission and assist pregnancy in HIV-discordant couples: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the effectiveness of semen washing in human immunodeficiency virus (HIV)-discordant couples in which the male partner is infected. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Forty single-arm open-label studies among HIV-discordant couples that underwent intrauterine insemination (IUI) or in vitro fertilization (IVF) with or without intracytoplasmic sperm injection (ICSI) using washed semen. INTERVENTION(S): Semen washing followed by IUI, IVF, or IVF/ICSI. PRIMARY OUTCOME: HIV transmission to HIV-uninfected women; secondary outcomes: HIV transmission to newborns and proportion of couples achieving a clinical pregnancy. RESULT(S): No HIV transmission occurred in 11,585 cycles of assisted reproduction with the use of washed semen among 3,994 women. Among the subset of HIV-infected men without plasma viral suppression at the time of semen washing, no HIV seroconversions occurred among 1,023 women after 2,863 cycles of assisted reproduction with the use of washed semen. Studies that measured HIV transmission to infants reported no cases of vertical transmission. Overall, 56.3% of couples (2,357/4,184) achieved a clinical pregnancy with the use of washed semen. CONCLUSION(S): Semen washing appears to significantly reduce the risk of transmission in HIV-discordant couples desiring children, regardless of viral suppression in the male partner. There are no randomized controlled studies or studies from low-income countries, especially those with a large burden of HIV. Continued development of lower-cost semen washing and assisted reproduction technologies is needed. Integration of semen washing into HIV prevention interventions could help to further reduce the spread of HIV.

A discussion of key values to inform the design and delivery of services for HIV-affected women and couples attempting pregnancy in resource-constrained settings.

INTRODUCTION: HIV-affected women and couples often desire children and many accept HIV risk in order to attempt pregnancy and satisfy goals for a family. Risk reduction strategies to mitigate sexual and perinatal HIV transmission include biomedical and behavioural approaches. Current efforts to integrate HIV and reproductive health services offer prime opportunities to incorporate strategies for HIV risk reduction during pregnancy attempts. Key client and provider values about services to optimize pregnancy in the context of HIV risk provide insights for the design and implementation of large-scale "safer conception" programmes. DISCUSSION: Through our collective experience and discussions at a multi-disciplinary international World Health Organization-convened workshop to initiate the development of guidelines and an algorithm of care to support the delivery of services for HIV-affected women and couples attempting pregnancy, we identified four values that are key to the implementation of these programmes: (1) understanding fertility care and an ability to identify potential fertility problems; (2) providing equity of access to resources enabling informed decision-making about reproductive choices; (3) creating enabling environments that reduce stigma associated with HIV and infertility; and (4) creating enabling environments that encourage disclosure of HIV status and fertility status to partners. Based on these values, recommendations for programmes serving HIV-affected women and couples attempting pregnancy include the following: incorporation of comprehensive reproductive health counselling; training to support the transfer and exchange of knowledge between providers and clients; care environments that reduce the stigma of childbearing among HIV-affected women and couples; support for safe and voluntary disclosure of HIV and fertility status; and increased efforts to engage men in reproductive decision-making at times that align with women's desires. CONCLUSIONS: Programmes, policies and guidelines that integrate HIV treatment and prevention, sexual and reproductive health and fertility care services in a manner responsive to user values and preferences offer opportunities to maximize demand for and use of these services. For HIV-affected women and couples attempting pregnancy, the provision of comprehensive services using available tools - and the development of new tools that are adaptable to many settings and follow consensus recommendations - is a public health imperative. The impetus now is to design and deliver value-driven inclusive programming to achieve the greatest coverage and impact to reduce HIV transmission during pregnancy attempts.

International Federation of Gynecology and Obstetrics opinion on reproductive health impacts of exposure to toxic environmental chemicals.

Exposure to toxic environmental chemicals during pregnancy and breastfeeding is ubiquitous and is a threat to healthy human reproduction. There are tens of thousands of chemicals in global commerce, and even small exposures to toxic chemicals during pregnancy can trigger adverse health consequences. Exposure to toxic environmental chemicals and related health outcomes are inequitably distributed within and between countries; universally, the consequences of exposure are disproportionately borne by people with low incomes. Discrimination, other social factors, economic factors, and occupation impact risk of exposure and harm. Documented links between prenatal exposure to environmental chemicals and adverse health outcomes span the life course and include impacts on fertility and pregnancy, neurodevelopment, and cancer. The global health and economic burden related to toxic environmental chemicals is in excess of millions of deaths and billions of dollars every year. On the basis of accumulating robust evidence of exposures and adverse health impacts related to toxic environmental chemicals, the International Federation of Gynecology and Obstetrics (FIGO) joins other leading reproductive health professional societies in calling for timely action to prevent harm. FIGO recommends that reproductive and other health professionals advocate for policies to prevent exposure to toxic environmental chemicals, work to ensure a healthy food system for all, make environmental health part of health care, and champion environmental justice.

Perinatal risk in singleton pregnancies after in vitro fertilization.

OBJECTIVE: To assess perinatal risks to singleton births after in vitro fertilization (IVF) versus spontaneous conception. DESIGN: Cross-sectional. SETTING: A 2006 registry database of the Japan Society of Obstetrics and Gynaecology (JSOG) capturing 5.8% of total births. PATIENT(S): 53,939 singleton births from spontaneous conceptions and 1,408 singletons after IVF. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Perinatal death, low-birth weight (LBW), small for gestational age (SGA), congenital malformation, and sex ratio assessment based on singleton birth cases versus singleton live-born cases. RESULT(S): In this study, IVF may include intracytoplasmic sperm injection (ICSI), gamete intrafallopian transfer, or IVF followed by zygote intrafallopian transfer. In crude and adjusted analysis, perinatal death, SGA, congenital malformation, and sex ratio were not statistically significantly associated with IVF. The LBW rates were statistically significantly higher in IVF pregnancies, but the association statistically significantly decreased after adjusting for confounding factors. Placental previa, a maternal outcome, was found to be statistically significantly higher in IVF pregnancies. CONCLUSION(S): No evidence was implicated IVF procedures as dramatically increasing the adjusted risk of perinatal death, LBW, SGA, congenital malformation, or sex ratio when compared with spontaneous conceptions. However, because of sample size limitations, the study cannot exclude small to moderate increases in perinatal deaths or congenital malformations.