P-652 Chronic kidney disease and female reproductive hormonal profile: A multi-centre cohort study
Authors: Bhaduri M , Wells H , Zimmerman K , Sarris I , Bramham K 
Published: July 2024

Abstract

Study question
Does Chronic Kidney Disease (CKD) impact female reproductive hormone profiles?

Summary answer
Women with CKD had significantly lower AMH and testosterone, and significantly higher LH levels. There were no differences in FSH, oestradiol, prolactin and progesterone.

What is known already
Chronic diseases, such as CKD, is rising in women of reproductive age. It is expected that the prevalence of CKD in adults will increase to 16.7% in 2030.Coupled with improvements in obstetric care and advancement in assisted reproductive technology, more women with CKD are seeking to conceive with ART. It is known that CKD reduces fertility, but underlying mechanisms are not fully understood. It is proposed that CKD leads to dysregulation of the hypothalamus-pituitary-ovarian (HPO) axis, but studies are small, use outdated assays, are done at different times in the menstrual cycle and do not compare with healthy controls.

Study design, size, duration
Observational cohort study involving women with CKD and healthy women of reproductive age without underlying medical conditions was conducted between August 2021-September 2022.Women with CKD were identified from four units to attend a study visit at a tertiary fertility unit.Healthy controls were recruited via word of mouth and from couples within the unit undergoing treatment for male factor infertility.For the study to be powered 100 women with CKD and 50 healthy controls were recruited.

Participants/materials, setting, methods
Ethical approval was provided by the Health Research Authority (IRAS 285546) and written informed consent was obtained from participants.Serum Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), prolactin, testosterone, oestradiol, progesterone, Anti Mullerian Hormone (AMH) and b-HCG were taken between the first and fifth day of menstrual cycle. If there was amennorhoea, bloods were taken on a day suiting them. Comparisons between controls and CKD Stage utilised t-test and Mann Whitney U tests according to data-distribution.

Main results and the role of chance
101 women with CKD and 63 healthy women were recruited. The mean age of women in the CKD group was 35.1± 6.7 years and of controls was 33.44 ±4.8 years, median BMI for CKD women was 25.45 kg/m2 (IQR 22.7,29.4) and controls was 24.5 kg/m2 (IQR 22,26.7).The renal cohort had similar numbers in each of the four CKD stages. 20.8% women had renal transplants.The two cohorts were matched for age and BMI.
Median AMH (13.6(IQR 3,4,28.7) vs 18.4 (IQR 11.2,33.6) pmol/L;p=0.03) was significantly lower in the renal group than controls. Median testosterone concentrations (0.6 (IQR 0.5,0.9) vs 0.5 (IQR 0.4,0.7)nmol/L; p = 0.01) were significantly lower in women with CKD even from stage 1 CKD.
LH (4.4 (IQR 3.2,5.5) vs 5.9 (IQR 3.8,9.4) IU/L;p=0.001) concentrations were significantly higher in women with CKD compared to controls but there were no differences in FSH, oestradiol, prolactin and progesterone. LH increased and testosterone and AMH concentrations fell with CKD severity. Interestingly, b-HCG was &gt;6 IU/L in 3.0% (3/101) patients with CKD.
When stratified by CKD stage; CKD stage 2 and onwards had significantly higher LH concentrations (p = 0.03).CKD stage 3 and above participants had significant lower AMH concentrations (p = 0.002).This is at a later stage of CKD than previously published.

Limitations, reasons for caution
Although this is the largest study of its kind known to explore female hormonal profiles in women with CKD, the numbers are still limited. In addition, our population had a mixed ethnic background but due to the small numbers we were unable to analyse the results per ethnic category.

Wider implications of the findings
This is the largest prospective study comparing fertility hormonal profiles in women with CKD and healthy controls. Unfortunately, there remains a paucity of evidence on the effects of CKD on female fertility. Future work includes exploring longitudinal changes which will better facilitate patients to make informed and timely fertility-related decisions.

Trial registration number
285546