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.

Comparing endometrial preparation methods in frozen embryo transfers - Does a previous live birth make a difference?

RESEARCH QUESTION: Does the outcome of a medicated or natural endometrial preparation for a frozen cycle differ if a patient has previously experienced a failed fresh cycle? DESIGN: Retrospective matched case-controlled study to investigate frozen embryo transfer (FET) outcomes in women undergone medicated or natural endometrial preparation, with adjustment to the history of previous live birth. 878 frozen cycles were included for analysis, over a period of 2 years. RESULTS: After adjusting for the number of embryos transferred, endometrial thickness and the number of previous embryo transfers, there was no difference in live birth rate (LBR) between medicated-FET and natural-FET groups regardless of the previous fertility outcome (p = 0.08). CONCLUSIONS: A previous live birth does not affect the outcome of a subsequent frozen cycle, regardless of whether medicated- or natural endometrial preparation is used.

Ethnic disparities in pregnancy-related acute kidney injury in a United Kingdom population.

BACKGROUND: The incidence of acute kidney injury in pregnancy (P-AKI) is rising and is associated with detrimental maternal and foetal outcomes. Ethnic disparities in pregnancy outcomes are well recognized, with females who identify as Black or Asian being more likely to die during pregnancy compared to females who identify as White ethnicity. METHODS: This study reports rates of P-AKI and associated risk factors in pregnant females of different ethnicities. All pregnancies were recorded between 2016 and 2020. AKI episodes were identified using electronic alerts. Ethnicity, AKI stage (1-3), obstetric outcomes and risk factors for P-AKI (chronic hypertension, pregnancy-induced hypertension and pre-eclampsia, and haemorrhage) were assessed. RESULTS: There were 649 P-AKI episodes from 16,943 deliveries (3.8%). Black females were more likely to have P-AKI (5.72%) compared to those who were White (3.12%), Asian (3.74%), mixed ethnicity (2.89%) and Other/Not Stated (3.10%). Black females, compared to White females, were at greater risk of developing P-AKI if they had haemorrhage requiring blood transfusion (OR 2.44, 95% CI 1.31,4.54; p < 0.001) or pregnancy-induced hypertension (OR 1.79, 95% CI 1.12, 2.86; p < 0.001). After adjusting for risk factors, Black females had increased risk of developing P-AKI (OR 1.52, 95% CI 1.22, 1.80; p < 0.001) compared to White females. Black females were at increased risk of developing P-AKI compared to White females. Mode of delivery, pregnancy-induced hypertension and haemorrhage are likely to have contributed. The increased risk persists despite accounting for these variables, suggesting that other factors such as socioeconomic disparities need to be considered. CONCLUSIONS: The incidence of P-AKI is likely higher than previously stated in the literature. However, caution must be exercised, particularly with AKI stage 1, as the KDIGO system is not validated in pregnancy and gestational changes in renal physiology need to be considered. Pregnancy-specific AKI definitions are needed.

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.

Acute kidney injury e-alerts in pregnancy: rates, recognition and recovery.

BACKGROUND: Acute kidney injury (AKI) in pregnancy (Pr-AKI) is associated with substantial maternal morbidity and mortality. E-alerts are routinely used for detection of AKI in non-pregnant patients but their role in maternity care has not been explored. METHODS: All pregnant or postpartum women with AKI e-alerts for AKI Stages 1-3 (Kidney Disease Improving Global Outcomes (KDIGO) criteria) were identified at a tertiary centre >2 years. Two women matched by delivery date for each case were selected as controls. AKI stage, recognition of AKI, pregnancy outcomes, renal recovery, AKI aetiology and risk factors were extracted from electronic patient records. RESULTS: 288 of 11 922 (2.4%) women had AKI e-alerts, of which only 118 (41%) were recognized by the obstetric team. Common Pr-AKI causes included infection (48%), pre-eclampsia (26%) and haemorrhage (25%), but no cause was identified in 15% of women. Renal function recovered in 213 (74%) women, but in 47 (17%) repeat testing was not undertaken and 28 (10%) did not recover function. Hypertensive disorders of pregnancy and Caesarean section were associated with increased incidence of Pr-AKI compared with controls. CONCLUSIONS: Pr-AKI e-alerts were identified in ∼1 in 40 pregnancies. However, a cause for Pr-AKI was not identified in many cases and e-alerts may have been triggered by gestational change in serum creatinine. Pregnancy-specific e-alert algorithms may be required. However, 1 in 10 women with Pr-AKI had not recovered kidney function on repeat testing. Better understanding of long-term impacts of Pr-AKI on pregnancy and renal outcomes is needed to inform relevant Pr-AKI e-alert thresholds.

Planned and unplanned pregnancies in breast cancer survivors.

BACKGROUND: Nearly 20% of women presenting with breast cancer in the UK are of reproductive age. The aim of our study was to assess fertility outcome in relation to intent to conceive in patients who had completed breast cancer treatment. METHODS: Between July 2011 and December 2013, women, aged less than 43 years at the time of diagnosis, were asked during their follow-up in breast cancer clinic, to complete a questionnaire on intentions to conceive and pregnancy outcome. RESULTS: A total of 175 women completed the questionnaire at a median time of 6 years from time of diagnosis. Their median age at the time of diagnosis was 37 years and at the time of the survey was 43 years. At the time of the survey, 42% (72/175) had completed their family, 41% (72/175) reported that they would like to have children and 4% (7/175) did not wish to have children. Twenty-seven respondents had actively tried to conceive, and of those 13 (48%) had a live birth. There were 12 unintended pregnancies; the majority of which were terminated (58% (7/12)) with only 3 live births. Among those who did not wish to conceive, only 32% (36/111) reported using contraception. CONCLUSION: This is a retrospective study investigating menstrual function, contraceptive methods and fertility outcomes of young breast cancer survivors. This study highlights the need for healthcare professionals to provide long-term contraceptive advice to women who do not wish to conceive.