Baseline anatomical assessment of the uterus and ovaries in infertile women: a systematic review of the evidence on which assessment methods are the safest and most effective in terms of improving fertility outcomes.

BACKGROUND: This review focuses on the initial presentation of women who suspect that they are infertile, and how best to assess the anatomy of their uterus and ovaries in order to investigate the cause of their infertility, and potentially improve desired fertility outcomes. This review was undertaken as part of a World Health Organization initiative to assess the evidence available to address guidance for the diagnosis and treatment of infertility within a global context. Providing access to care for infertile women will help to ease the psycho-social burdens, such as ostracization, intimate partner violence and other negative consequences of being involuntarily childless or unable to become pregnant despite desiring a biological child or children. OBJECTIVE AND RATIONALE: The aim of this paper was to present an evidence base for the diagnostic and prognostic value of various investigations used for detecting uterine and/or ovarian pathology in women presenting at fertility clinics for their initial assessment. SEARCH METHODS: We performed a comprehensive search of relevant studies on 28 August and 10 September 2014. A further search was performed on 6 June 2016 to ensure all possible studies were captured. These strategies were not limited by date or language. The search returned 3968 publications in total; 63 full text articles were retrieved and 10 additional studies were found through hand-searching. After excluding 54, a total of 19 studies were analysed. We extracted and tabulated data on the characteristics, quality and results of each eligible study and combined the findings in a narrative synthesis. Risk of bias was assessed according to article type using tools such as assessment of the methodological quality of systematic reviews, Newcastle Ottawa Scale, Cochrane risk of bias tool, quality assessment tool for diagnostic accuracy studies and quality in prognostic studies. Nineteen studies were selected as being the best evidence available. A narrative synthesis of the data was undertaken. Discussion of the data, and resultant consensus for best practice were accomplished in a consensus expert consultation in Geneva, October 2015. An independent expert review process concerning this work and outcomes was conducted during 2016. OUTCOMES: The draft recommendations presented here apply to infertile women whether or not they are undergoing fertility treatment. Transvaginal ultrasound (TVUS) should be offered to all infertile women with symptoms or signs of anatomic pelvic pathology. TVUS should not be offered routinely to women without symptoms of pelvic pathology. Hysteroscopy should be offered if intrauterine pathology is suspected by TVUS. Hysteroscopy should not be routinely offered to infertile women who have normal TVUS findings. In women who have normal TVUS findings and are undergoing IVF, hysteroscopy does not improve the outcome. Good practice points recommend that providers of fertility care should confirm that all infertile women have a recent pelvic examination, recent cervical screening and well-woman screening in line with local guidelines. Additionally, hystero-contrast salpingography in infertile women does not improve clinical pregnancy rates with expectant management in heterosexual couples and should not be offered as a therapeutic procedure. Most of the findings of this review on diagnosis are based on a low, or very low, quality of evidence, according to GRADE Working Group (grading of recommendations, assessment, development and evaluation) criteria. A low quality grading indicates that further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate, while a very low grade indicates that any estimate of effect is very uncertain. WIDER IMPLICATIONS: This review provides the most reliable evidence available to guide clinicians worldwide in the initial, evidence-based investigation of women with fertility problems in order to undertake the most useful investigation and avoid the burden of unnecessary tests.

Oocyte, embryo and blastocyst cryopreservation in ART: systematic review and meta-analysis comparing slow-freezing versus vitrification to produce evidence for the development of global guidance.

BACKGROUND: Successful cryopreservation of oocytes and embryos is essential not only to maximize the safety and efficacy of ovarian stimulation cycles in an IVF treatment, but also to enable fertility preservation. Two cryopreservation methods are routinely used: slow-freezing or vitrification. Slow-freezing allows for freezing to occur at a sufficiently slow rate to permit adequate cellular dehydration while minimizing intracellular ice formation. Vitrification allows the solidification of the cell(s) and of the extracellular milieu into a glass-like state without the formation of ice. OBJECTIVE AND RATIONALE: The objective of our study was to provide a systematic review and meta-analysis of clinical outcomes following slow-freezing/thawing versus vitrification/warming of oocytes and embryos and to inform the development of World Health Organization guidance on the most effective cryopreservation method. SEARCH METHODS: A Medline search was performed from 1966 to 1 August 2016 using the following search terms: (Oocyte(s) [tiab] OR (Pronuclear[tiab] OR Embryo[tiab] OR Blastocyst[tiab]) AND (vitrification[tiab] OR freezing[tiab] OR freeze[tiab]) AND (pregnancy[tiab] OR birth[tiab] OR clinical[tiab]). Queries were limited to those involving humans. RCTs and cohort studies that were published in full-length were considered eligible. Each reference was reviewed for relevance and only primary evidence and relevant articles from the bibliographies of included articles were considered. References were included if they reported cryosurvival rate, clinical pregnancy rate (CPR), live-birth rate (LBR) or delivery rate for slow-frozen or vitrified human oocytes or embryos. A meta-analysis was performed using a random effects model to calculate relative risk ratios (RR) and 95% CI. OUTCOMES: One RCT study comparing slow-freezing versus vitrification of oocytes was included. Vitrification was associated with increased ongoing CPR per cycle (RR = 2.81, 95% CI: 1.05-7.51; P = 0.039; 48 and 30 cycles, respectively, per transfer (RR = 1.81, 95% CI 0.71-4.67; P = 0.214; 47 and 19 transfers) and per warmed/thawed oocyte (RR = 1.14, 95% CI: 1.02-1.28; P = 0.018; 260 and 238 oocytes). One RCT comparing vitrification versus fresh oocytes was analysed. In vitrification and fresh cycles, respectively, no evidence for a difference in ongoing CPR per randomized woman (RR = 1.03, 95% CI: 0.87-1.21; P = 0.744, 300 women in each group), per cycle (RR = 1.01, 95% CI: 0.86-1.18; P = 0.934; 267 versus 259 cycles) and per oocyte utilized (RR = 1.02, 95% CI: 0.82-1.26; P = 0.873; 3286 versus 3185 oocytes) was reported. Findings were consistent with relevant cohort studies. Of the seven RCTs on embryo cryopreservation identified, three met the inclusion criteria (638 warming/thawing cycles at cleavage and blastocyst stage), none of which involved pronuclear-stage embryos. A higher CPR per cycle was noted with embryo vitrification compared with slow-freezing, though this was of borderline statistical significance (RR = 1.89, 95% CI: 1.00-3.59; P = 0.051; three RCTs; I2 = 71.9%). LBR per cycle was reported by one RCT performed with cleavage-stage embryos and was higher for vitrification (RR = 2.28; 95% CI: 1.17-4.44; P =  0.016; 216 cycles; one RCT). A secondary analysis was performed focusing on embryo cryosurvival rate. Pooled data from seven RCTs (3615 embryos) revealed a significant improvement in embryo cryosurvival following vitrification as compared with slow-freezing (RR = 1.59, 95% CI: 1.30-1.93; P < 0.001; I2 = 93%). WIDER IMPLICATIONS: Data from available RCTs suggest that vitrification/warming is superior to slow-freezing/thawing with regard to clinical outcomes (low quality of the evidence) and cryosurvival rates (moderate quality of the evidence) for oocytes, cleavage-stage embryos and blastocysts. The results were confirmed by cohort studies. The improvements obtained with the introduction of vitrification have several important clinical implications in ART. Based on this evidence, in particular regarding cryosurvival rates, laboratories that continue to use slow-freezing should consider transitioning to the use of vitrification for cryopreservation.

Not the usual suspects: addressing layers of vulnerability.

This paper challenges the traditional account of vulnerability in healthcare which conceptualizes vulnerability as a list of identifiable subpopulations. This list of 'usual suspects', focusing on groups from lower resource settings, is a narrow account of vulnerability. In this article we argue that in certain circumstances middle-class individuals can be also rendered vulnerable. We propose a relational and layered account of vulnerability and explore this concept using the case study of cord blood (CB) banking. In the first section, two different approaches to 'vulnerability' are contrasted: categorical versus layered. In the second section, we describe CB banking and present a case study of CB banking in Argentina. We examine the types of pressure that middle-class pregnant women feel when considering CB collection and storage. In section three, we use the CB banking case study to critique the categorical approach to vulnerability: this model is unable to account for the ways in which these women are vulnerable. A layered account of vulnerability identifies several ways in which middle-class women are vulnerable. Finally, by utilizing the layered approach, this paper suggests how public health policies could be designed to overcome vulnerabilities.