Female Infertility in Chronic Kidney Disease.

This review summarises the current literature regarding infertility in women with chronic kidney disease (CKD), describing the epidemiology, pathophysiology, investigations, and management options. The pathophysiology is multifactorial, with proposed mechanisms including disruption of the hypothalamus-pituitary-ovarian axis, chronic inflammation, oxidative stress, psychological factors, and gonadotoxic effects of medications such as cyclophosphamide. Diagnostic investigations in CKD patients seeking to conceive should be considered earlier than in the healthy population. Investigations should include hormonal profiling, including markers such as Anti-Mullerian Hormone and imaging such as ultrasound, to evaluate ovarian reserve and identify gynaecology pathology. Treatment options for infertility in CKD patients include GnRH agonists to preserve ovarian function during cyclophosphamide treatment, as well as assisted reproductive technologies including in vitro fertilisation and ovulation induction. However, these treatments must be tailored to the individual's health status, comorbidities, fertility requirements, and CKD stage. In conclusion, fertility is an important consideration for women with CKD, necessitating early investigation and tailored management. Early discussions regarding fertility are important in order to understand patients' family planning and allow for prompt referral to fertility services. While challenges exist, ongoing research aims to clarify the underlying mechanism and optimise treatment strategies, which are crucial for improving quality of life and overall health outcomes.

Effect of female body mass index on intrauterine insemination outcomes: a systematic review and meta-analysis.

The prevalence of women with a raised body mass index (BMI) seeking assisted conception treatment is increasing. Findings of existing studies evaluating the effect of female BMI on intrauterine insemination (IUI) treatment outcomes remain inconsistent. This systematic review and meta-analysis evaluate the effect of female BMI on IUI treatment outcomes. Two authors independently conducted data extraction and assessed study quality. Risk ratios (RR) and 95% confidence intervals were calculated using the Mantel-Haenszel approach for dichotomous outcomes. 11 studies involving 23,145 IUI treatment events, comprising 21,211 cycles from 8 studies, and 1,934 participants in three studies, met the inclusion criteria for the meta-analysis. Two cohorts of women undergoing IUI treatment were compared - women with normal BMI < 25 kg/m2 were compared with a second cohort of women with a BMI category ≥ 25 kg/m2. There was no statistically significant difference in live birth rate (LBR) (RR 1.06, 95% CI 0.86-1.307); clinical pregnancy rate (CPR) (RR 0.94, 95% CI 0.78-1.13); miscarriage (RR 0.92, 95% CI 0.31-2.74) or ectopic pregnancy rate (RR 2.20, 95% CI 0.78-6.23). Our meta-analysis showed that a raised female BMI did not affect IUI treatment outcomes. Nevertheless, weight loss counselling should be offered to women with a raised BMI undergoing IUI, to reduce the associated obstetric morbidity.

A meta-analysis of 11 studies found that having a raised female BMI did not change IUI treatment outcomes.

Systematic review of pregnancy and renal outcomes for women with chronic kidney disease receiving assisted reproductive therapy.

BACKGROUND: As awareness around infertility is increasing among patients with chronic kidney disease (CKD), ever more of them are seeking Assisted Reproductive Technology (ART). Our aim was to perform a systematic review to describe obstetric and renal outcomes in women with CKD following ART. METHODS: The following databases were searched from 1946 to May 2021: (1) Cochrane Central Register of Controlled Trials (CENTRAL), (2) Cumulative Index to Nursing and Allied Health Literature (CINAHL), (3) Embase and (4) MEDLINE. RESULTS: The database search identified 3520 records, of which 32 publications were suitable. A total of 84 fertility treatment cycles were analysed in 68 women. Median age at time of pregnancy was 32.5 years (IQR 30.0, 33.9 years). There were 60 clinical pregnancies resulting in 70 live births (including 16 multifetal births). Four women developed ovarian hyperstimulation syndrome which were associated with acute kidney injury. Hypertensive disorders complicated 26 pregnancies (38.3%), 24 (35.3%) pregnancies were preterm delivery, and low birth weight was present in 42.6% of pregnancies. Rates of live birth and miscarriage were similar for women with CKD requiring ART or having natural conception. However, more women with ART developed pre-eclampsia (p < 0.05) and had multifetal deliveries (p < 0.001), furthermore the babies were lower gestational ages (p < 0.001) and had lower birth weights (p < 0.001). CONCLUSION: This systematic review represents the most comprehensive assessment of fertility outcomes in patients with CKD following ART. However, the high reported live birth rate is likely related to reporting bias. Patient selection remains crucial in order to maximise patient safety, screen for adverse events and optimise fertility outcomes.

Protocol for developing a core outcome set for male infertility research: an international consensus development study.

STUDY QUESTION: We aim to develop, disseminate and implement a minimum data set, known as a core outcome set, for future male infertility research. WHAT IS KNOWN ALREADY: Research into male infertility can be challenging to design, conduct and report. Evidence from randomized trials can be difficult to interpret and of limited ability to inform clinical practice for numerous reasons. These may include complex issues, such as variation in outcome measures and outcome reporting bias, as well as failure to consider the perspectives of men and their partners with lived experience of fertility problems. Previously, the Core Outcome Measure for Infertility Trials (COMMIT) initiative, an international consortium of researchers, healthcare professionals and people with fertility problems, has developed a core outcome set for general infertility research. Now, a bespoke core outcome set for male infertility is required to address the unique challenges pertinent to male infertility research. STUDY DESIGN SIZE DURATION: Stakeholders, including healthcare professionals, allied healthcare professionals, scientists, researchers and people with fertility problems, will be invited to participate. Formal consensus science methods will be used, including the modified Delphi method, modified Nominal Group Technique and the National Institutes of Health's consensus development conference. PARTICIPANTS/MATERIALS SETTING METHODS: An international steering group, including the relevant stakeholders outlined above, has been established to guide the development of this core outcome set. Possible core outcomes will be identified by undertaking a systematic review of randomized controlled trials evaluating potential treatments for male factor infertility. These outcomes will be entered into a modified Delphi method. Repeated reflection and re-scoring should promote convergence towards consensus outcomes, which will be prioritized during a consensus development meeting to identify a final core outcome set. We will establish standardized definitions and recommend high-quality measurement instruments for individual core outcomes. STUDY FUNDING/COMPETING INTERESTS: This work has been supported by the Urology Foundation small project award, 2021. C.L.R.B. is the recipient of a BMGF grant and received consultancy fees from Exscentia and Exceed sperm testing, paid to the University of Dundee and speaking fees or honoraria paid personally by Ferring, Copper Surgical and RBMO. S.B. received royalties from Cambridge University Press, Speaker honoraria for Obstetrical and Gynaecological Society of Singapore, Merk SMART Masterclass and Merk FERRING Forum, paid to the University of Aberdeen. Payment for leadership roles within NHS Grampian, previously paid to self, now paid to University of Aberdeen. An Honorarium is received as Editor in Chief of Human Reproduction Open. M.L.E. is an advisor to the companies Hannah and Ro. B.W.M. received an investigator grant from the NHMRC, No: GNT1176437 is a paid consultant for ObsEva and has received research funding from Ferring and Merck. R.R.H. received royalties from Elsevier for a book, consultancy fees from Glyciome, and presentation fees from GryNumber Health and Aytu Bioscience. Aytu Bioscience also funded MiOXYS systems and sensors. Attendance at Fertility 2020 and Roadshow South Africa by Ralf Henkel was funded by LogixX Pharma Ltd. R.R.H. is also Editor in Chief of Andrologia and has been an employee of LogixX Pharma Ltd. since 2020. M.S.K. is an associate editor with Human Reproduction Open. K.Mc.E. received an honoraria for lectures from Bayer and Pharmasure in 2019 and payment for an ESHRE grant review in 2019. His attendance at ESHRE 2019 and AUA 2019 was sponsored by Pharmasure and Bayer, respectively. The remaining authors declare no competing interests. TRIAL REGISTRATION NUMBER: Core Outcome Measures in Effectiveness Trials (COMET) initiative registration No: 1586. Available at www.comet-initiative.org/Studies/Details/1586. TRIAL REGISTRATION DATE: N/A. DATE OF FIRST PATIENT'S ENROLMENT: N/A.

The impact of emotional health on assisted reproductive technology outcomes: a systematic review and meta-analysis.

This systematic review and meta-analysis has addressed ongoing controversy surrounding the association between pre-treatment anxiety, stress and depression and assisted reproductive technology (ART) outcomes. Medline, Embase and PsycINFO were searched up to November 2019. The eligibility criterion was observational studies reporting the association between pre-treatment anxiety, stress or depression and ART outcomes in men, women or couples undergoing ART. The association between pre-treatment anxiety, stress and depression and ART outcomes were extracted, and meta-analyses carried out if ≥3 studies assessed the same outcome over the same number of cycles and reported results homogeneously. The review reports a potential association between decreased sperm motility and increased male state anxiety, but no significant association between women's pre-treatment emotional health and ART outcomes in terms of live birth, clinical pregnancy, chemical pregnancy, oocyte retrieval, embryos transferred or fertilization. Meta-analyses showed no significant standardized mean difference (SMD) for anxiety/stress and clinical or chemical pregnancy, or depression and clinical or chemical pregnancy.

Risk of breast cancer in women treated with ovarian stimulation drugs for infertility: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the evidence addressing the association between the use of ovarian stimulation drugs and the risk of breast cancer. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Women without any previous history of breast cancer undergoing ovarian stimulation. INTERVENTION(S): Electronic databases were searched from 1990 until January 2020. All cohort studies reporting new incidences of breast cancer in infertile women using ovarian stimulating drugs were included. Treated (exposed) infertile women were compared with the unexposed general population with unexposed infertile women as controls. MAIN OUTCOME MEASURE(S): New diagnosis of breast cancer within an infertile and general population after exposure to ovarian stimulation drugs. RESULT(S): Overall, the quality of evidence was very low because of the serious risk of bias and indirectness (nonrandomized studies). There was no significant increase in the risk of breast cancer among women treated with any ovarian stimulation drug for infertility compared with that in unexposed controls from the general population and the infertile population (pooled odds ratio 1.03, 95% Confidence interval 0.86 to 1.23, 20 studies, I2 = 88.41%, very low quality of evidence). Furthermore, no significant increase in the risk of breast cancer was found with the use of clomiphene citrate or gonadotropins, alone or in combination. CONCLUSION(S): The current study found that the use of clomiphene citrate and gonadotropins in infertile women was not associated with an increased risk of breast cancer.

Evaluation of healthcare professionals' understanding of eponymous maneuvers and mnemonics in emergency obstetric care provision.

OBJECTIVE: To evaluate whether eponymous maneuvers and mnemonics taught for the management of shoulder dystocia, vaginal breech delivery, and uterine inversion were remembered and understood in practice. METHODS: A questionnaire was distributed to obstetricians and midwives collecting information about the HELPERR and PALE SISTER mnemonics. Three extended matching questions evaluated participants' knowledge of the correct maneuvers, with their matching eponyms, used in the management of shoulder dystocia, vaginal breech delivery, and uterine inversion. RESULTS: Of the 112 participants, 90% were familiar with the HELPERR mnemonic, with 79% using it in their practice. Of those who used it, only 32% could correctly decipher it (P = 0.032). PALE SISTER was mostly unfamiliar. The percentages of correct maneuvers used for managing shoulder dystocia, breech delivery, and uterine inversion were 84.6%, 58.3%, and 28.6%, respectively. However, the eponyms were correctly matched to their maneuvers in only 33.3%, 14.3%, and 0% of cases, respectively (P < 0.01). CONCLUSION: The meanings of the mnemonics for obstetric emergencies were frequently recalled incorrectly. This, together with the poor correlation between knowledge of maneuvers and their eponyms, limits their usefulness and indicates that teaching should focus on learning without relying on mnemonics and eponyms.

A longitudinal study of normal fetal femur volume.

OBJECTIVE: Fetal femur volume (FV) is a useful marker of skeletal growth. Our objective was to create a normal FV chart in a cohort of healthy pregnant women and to assess FV repeatability. METHOD: The method used was a prospective, observational study using 3D ultrasound. Low-risk pregnant women underwent serial scans from 14 to 42 weeks. Strict inclusion and exclusion criteria were used in order to remove pathological conditions. Pregnancies were dated by last menstrual period and confirmed by crown-rump length. FV was measured using three linear measurements and a volume equation. Data were analyzed using multilevel modeling. Repeatability was assessed using within-subject coefficients of variation (CV), intraclass correlation coefficients (ICC), and Bland-Altman plots. RESULTS: A total of 180 women underwent 868 scans, a median of five scans per participant. Median and centile values were presented in the form of curves, regression equations, and table of values per completed week. Intra-observer CV and ICC were 10.5% and 0.977, respectively; interobserver CV and ICC were 16.8% and 0.923. CONCLUSION: This normal FV chart can be used as a prescriptive standard in order to assess fetal skeletal growth. Measurement repeatability is satisfactory for clinical use, but FV has a larger random error than commonly seen with standard 2D biometry.

Sphenoidal fontanelle area measurement on rendered three-dimensional ultrasound.

OBJECTIVE: Rendered three-dimensional images of the fetal cranial vault permit the identification of sutures and measurement of the fontanelle surface area. The objective of this study was to establish the feasibility and repeatability of sphenoidal fontanelle area measurement. METHOD: Head volumes were obtained using the biparietal diameter as the reference plane. These were displayed with maximum rendering and the surface area of the sphenoidal fontanelle was measured by one operator. Feasibility was expressed as the percentage of scans with a successful measurement at different gestational ages. Repeatability was expressed as coefficient of variation (CV), intraclass correlation coefficient (ICC) and Bland-Altman plots. RESULTS: Thirty women underwent 141 scans. Feasibility of sphenoidal fontanelle measurement is over 90% before 26 weeks, but drops gradually thereafter and becomes 0% at 34 weeks. Intraobserver repeatability of measurement on the same scan image demonstrated CV = 17.5% and ICC = 0.883; however, when measuring a newly acquired volume, the repeatability is poor, CV = 30.7% and ICC = 0.649. CONCLUSION: Although it is feasible to visualize the sphenoidal fontanelle on rendered three dimensions, its surface area measurement is not reliable for clinical use. There is potential to overestimate repeatability when remeasuring the same volume.

White blood cell count as a predictor of the severity of sickle cell disease during pregnancy.

OBJECTIVE: Increasing epidemiological evidence implicates leukocytosis as a major risk factor for poor outcome in non-pregnant sickle cell disease (SCD) patients. The aim of this study was to investigate whether steady-state white blood cell (WBC) count can predict SCD-related problems in pregnancy. DESIGN: Retrospective observational study of 40 SCD pregnant women who had their antenatal care at Guy's & St Thomas' NHS Trust, London. Twenty-six women developed clinical complications related to SCD during their pregnancy (painful crisis, chest symptoms, infections, severe anaemia requiring blood transfusion, pre-eclampsia, and/or thromboembolism) and 14 remained asymptomatic. The steady-state leukocyte counts early in pregnancy were compared between the two groups and receiver operator characteristics (ROC) curve was plotted for different values of WBC. RESULTS: Compared to asymptomatic patients, women who developed SCD-related complications had significantly higher total WBC count [11.2 x 10(9)L(-1) (SD 3.22) versus 8 x 10(9)L(-1) (2.8), p<0.01], higher lymphocyte count [3 x 10(9)L(-1) (1.62) versus 1.6 x 10(9)L(-1) (0.65), p<0.01] and higher monocyte count [0.8 x 10(9)L(-1) (0.47) versus 0.4 x 10(9)L(-1) (0.21), p<0.01]. The neutrophil count showed a similar trend but the difference did not reach statistical significance [6.6 x 10(9)L(-1) (2.29) versus 5.7 x 10(9)L(-1) (2.15), p=0.22]. The area under the ROC curve was 74% (95% CI: 56-92). CONCLUSION: WBC count early in pregnancy was significantly higher in women who subsequently developed clinical problems related to SCD. The WBC may be used as a predictor of the severity of SCD in pregnancy.