Reproductive Health in Chronic Kidney Disease:

The Implications of Sex and Gender

Sandra M. Dumanski, MD, MSc *,†,‡ Dag Eckersten, MD, PhD § and
Giorgina Barbara Piccoli, MDII

Summary
Chronic kidney disease (CKD) is frequently accompanied by reproductive health challenges in females and males
alike. Progression of CKD is associated with escalating impairment of the hypothalamic−pituitary−gonadal axis,
which facilitates evolving ovarian, testicular, and sexual dysfunction. Common clinical reproductive health complica-
tions in CKD include abnormal menstruation, impaired sexual health, and reduced fertility. Though sex-specific fac-
tors, such as sex hormones and gonadal function, have a strong influence on reproductive health outcomes in
CKD, a person’s gender and gendered experience also have important implications. Institutionalized gender, gen-
dered perceptions of health, and health care−seeking behaviors, as well as adherence to medical care, all have crit-
ical effects on reproductive health in CKD. This review endeavors to explore the implications of both sex and gender
on overall reproductive health in individuals living with CKD.
Semin Nephrol 42:142−152 Ó 2022 Elsevier Inc. All rights reserved.
Keywords: Kidney, hormone, reproductive, fertility, sex, gender

but also by their gender.12 Gender is a sociocultural con-

T
he estimated global prevalence of chronic kidney
disease (CKD) is greater than 13% and is increas-
ing over time.1,2 Although traditionally consid-
ered a disease of older adults, individuals of all ages are
affected and the prevalence may be higher in females.1
CKD is accompanied by marked reproductive health
challenges for both females and males.3-5 Reproductive
health is defined by the World Health Organization as
follows: a state of complete physical, mental, and social
well-being and not merely the absence of disease or infir-
mary, in all matters relating to the reproductive system
and to its functions and processes.6 Common reproduc-
tive health abnormalities in CKD involve the dysregula-
tion of sex hormones, gonadal dysfunction, and sexual
dysfunction; which manifest clinically as abnormal men-
struation, impaired sexual health, and reduced fertility.3
Though reproductive health abnormalities specifically
related to sex hormone derangements appear to increase
in severity along the stages of CKD,7 dysfunctional
reproductive health has been reported even in early
stages of CKD.8-11
Reproductive health is influenced not only by an indi-
vidual’s biological sex (being male, female, or intersex),
*Department of Medicine, Cumming School of Medicine, University of
Calgary, Calgary, Canada
yLibin Cardiovascular Institute, Calgary, Canada
zAlberta Kidney Disease Network, Alberta, Canada
xDepartment of Nephrology, Lund University, Skane University Hos-
pital, Malmo, Sweden
kNephrologie, Centre Hospitalier Le Mans, Le Mans, France
Financial disclosure and conflict of interest statements: none.
Address reprint requests to Sandra M. Dumanski, MD, MSc, Section of
Nephrology, Cumming School of Medicine, University of Calgary,
1403-29th St NW, Calgary, Alberta, Canada T2N 2T9. E-mail:
sandra.dumanski@albertahealthservices.ca
0270-9295/ - see front matter
© 2022 Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.semnephrol.2022.04.005
struct, and describes the identities, expression, and roles
of boys/men, girls/women, and gender-diverse individu-
als. Although it is clear that sex-related factors, such as
sex hormones and gonadal function, have an important
impact on reproductive health in CKD; it also is critical
to recognize that gender-related factors, such as percep-
tions of health and stigma, health care−seeking behav-
iors, adherence to medical care, and gendered disparities
within the socioeconomic determinants of health, also
may play an important role.12,13
This review addresses the landscape of CKD-related
reproductive abnormalities, and adds to the current liter-
ature in its focus on the implications of not only sex, but
also of gender, on reproductive health in people living
with CKD.
SEX HORMONES, GONADAL FUNCTION, AND CKD
Female Sex Hormones
Kidney dysfunction appears to interfere with the normal
regulation of the hypothalamic−pituitary−ovarian hor-
mone axis in females.14 Although the vast majority of
sex hormone research to date has been completed in
individuals with advanced stages of CKD, specifically
dialysis-dependent CKD in which severe hormone dis-
turbances are shown, an increasing severity of hormone
disruption is surmised to be associated with progression
of CKD through the stages.7,14,15
In normal female physiology, the menstrual cycle
begins with the hypothalamus releasing pulses of gonad-
otropin-releasing hormone (GnRH), which in turn stimu-
lates release of follicle-stimulating hormone (FSH) from
the anterior pituitary gland.16 FSH induces ovarian folli-
culogenesis, resulting in progressively increasing levels
of estrogen, thereby triggering a midcycle surge of

142 Seminars in Nephrology, Vol 42, No 2, March 2022, pp 142−152

Reproductive Health in CKD
luteinizing hormone (LH) from the anterior pituitary
gland via further release of GnRH. This rapid increase in
LH level induces ovulation and release of the oocyte into
the fallopian tube. After ovulation, the corpus luteum is
created and secretes progesterone and estrogen, which
inhibits further release of gonadotropins. As the corpus
luteum degrades, however, estrogen and progesterone
levels decrease, resulting in stimulation of further GnRH
release, and the cycle begins again. Throughout this
cycle, anti-M€ullerian hormone (AMH) is released at a
consistent rate by preantral and antral ovarian follicles,
with the level of AMH being closely tied to the individu-
al’s ovarian reserve.17 In addition, the anterior pituitary
gland releases prolactin (PRL), which plays a role in
ovulation inhibition.18
Proposed mechanisms of female sex hormone
derangements in CKD are shown in Figure 1. Although
we describe the most severe pattern of hypothalamic
−pituitary−ovarian disruption in CKD below, it is impor-
tant to recognize that the degree of hormonal
Figure 1. The hypothalamic−pituitary−ovarian axis in females with chronic kidney disease (CKD). Reprinted with
permission from Dumanski et al.3 Abbreviations: FSH, follicle-stimulating hormone; GnRH, gonadotropin-releasing
hormone; LH, luteinizing hormone.
143
derangement is very variable in all CKD stages, perhaps
best demonstrated by the possibility of spontaneous preg-
nancy in females treated with dialysis.19 Furthermore,
hormone derangements already may be demonstrated in
early stages of CKD, however, the role of comorbidities
(eg, diabetes, obesity, recurrent infections) and associated
treatments (eg, immunosuppression, antihypertensive
drugs) are difficult to assess.20,21 A thorough understand-
ing of the female sex hormone variability in CKD is
made more difficult because of the relative paucity of
studies on female reproductive health in CKD.
In CKD, females may experience a marked
impairment of the pulsatile release of GnRH, which
leads to absent cyclicity of both FSH and LH, although
LH levels remain increased.14,22,23 In turn, estrogen lev-
els consistently are suppressed with no cyclicity, leading
to dysfunctional estrogen-related feedback to the hypo-
thalamus and anterior pituitary, thereby inhibiting the
LH surge.24 The culmination of persistent hypoestroge-
nemia and increased gonadotropin levels, alongside the
144
lack of cyclicity in sex hormone release, results in anov-
ulation and persistent hypoprogestinemia. Furthermore,
females with CKD may have increased levels of PRL,
secondary not only to reduced kidney clearance, but also
to increased production for reasons of reduced sensitivity
to dopaminergic inhibition.25 This elevation in PRL also
may contribute to the anovulatory state frequently
observed in advanced CKD.23,26 Finally, females with
CKD have a pronounced reduction in AMH levels com-
pared with their healthy counterparts, which already is
apparent in early stages of CKD.10,27 Conflicting data on
AMH levels are reported in females treated with dialysis;
earlier studies suggested an increased level, postulated
secondary to reduced kidney clearance,28,29 but more
contemporary studies have reported a reduced level in
this population.10,27
Interestingly, despite the severity of hypothalamic
−pituitary−ovarian effects in CKD, the female sex hor-
mone disruption appears to be largely reversible.
Although no studies specifically have addressed a func-
tional assessment of the hypothalamic−pituitary−ovar-
ian axis with intensive hemodialysis, a report of seven
females shifted to intensive from conventional hemodial-
ysis reported that intensive hemodialysis was associated
with a return of menses in two of three amenorrheic
females younger than age 40 years,23 suggesting
improvement of the sex hormone milieu. Furthermore,
kidney transplantation has been associated with
improvement or normalization of female sex hormone
levels, and is particularly evident in previously amenor-
rheic females.30,31 In a small prospective study, Wang et
al30 reported normalization of PRL, LH, FSH, and estro-
gen levels in all cases (32 females) within the first year
after kidney transplantation. Data on AMH levels after
kidney transplantation are of nonunivocal interpretation:
a reduction in AMH level post-transplantation has been
observed in some studies,28,29 but may be related to the
retention of AMH in dialysis patients; further studies are
needed to address the behavior of this important fertility
marker in females with CKD.
Female Ovarian Function
Hypothesized to be driven primarily by hypothalamic
−pituitary−ovarian axis disruption, many females with
CKD report abnormal menstruation.14,15,32 An early
study by Lim et al14 examined menstruation in females
with CKD, assessing menstrual bleeding patterns in 17
premenopausal females initiating hemodialysis. Only
one participant reported normal menstruation, 10
reported completely absent menstruation, and the
remainder reported abnormal patterns of menstruation,
such as irregular or heavy menstrual bleeding. Subse-
quent observational studies and surveys15,32 have con-
firmed these findings, reporting abnormal menstruation
in 75% to 85% of premenopausal females with CKD
S.M. Dumanski, D. Eckersten, and G.B. Piccoli
treated with dialysis, and absent menstruation in nearly
half of the cases. Aligned with the progression of female
sex hormone disruption, the prevalence of abnormal and
absent menstruation increases with CKD progression.33
Despite the severity of abnormal menstruation in the
CKD population, the endometrial response to estrogen
appears to be maintained in females with CKD who
menstruate.32
The diminished levels of AMH in females with CKD
suggests a reduction in the follicular pool in this popula-
tion.34 Correspondingly, the average age of menopause,
defined as the cessation of menses for 1 year,35 occurs
5 years earlier in females with CKD compared with the
general population.15,33,36 However, a functional meno-
pause has been reported in CKD, evidenced by the rever-
sal of menopause and resumption of menstruation in
some females treated with intensive hemodialysis or
kidney transplantation.23,36,37 Consequently, it remains
unclear as to how best to define permanent menopause in
the CKD population.24
Male Sex Hormones
Similar to their female counterparts, in males the hypo-
thalamic−pituitary−testicular axis may be disrupted as a
result of CKD, with the severity of the hormone distur-
bances roughly corresponding to the severity of kidney
dysfunction.22,38,39
In normal male physiology, pulsatile release of GnRH
from the hypothalamus stimulates release of LH and
FSH from the anterior pituitary, likewise in a pulsatile
fashion.40 LH binds to receptors in the Leydig cells of
the testis, thereby stimulating testosterone production.9
Synthesized testosterone is released, and acts directly on
the Sertoli cells of the testis to stimulate and regulate
spermatogenesis.41 Testosterone, through a negative
feedback mechanism, also provides inhibition of both
the hypothalamus and pituitary gland. FSH release from
the anterior pituitary binds to receptors on the Sertoli
cells of the testis, resulting in augmentation of spermato-
genesis, which is regulated primarily by testosterone.
The Sertoli cells also secrete AMH and Inhibin B; AMH
is postulated to have an autocrine function to modulate
spermatogenesis, and Inhibin B is responsible for FSH
inhibition.41 In addition, the anterior pituitary gland syn-
thesizes and releases PRL, a hormone important in male
sexual function, thought to play a role in regulation of
testosterone production and suppression of gonadotropin
release.42
Proposed mechanisms of male sex hormone disrup-
tions in CKD are shown in Figure 2. Similar to females,
there is wide variability of hormonal derangements in
males with CKD, although we describe the most severe
pattern of hypothalamic−pituitary−testicular disruption
here. In CKD, the hypothalamic GnRH pulses are
severely impaired and reduced in amplitude, resulting in
Reproductive Health in CKD
Figure 2. The hypothalamic−pituitary−testicular axis in males with chronic kidney disease (CKD). Abbreviations: AMH,
anti-Mullerian hormone; FSH, follicle-stimulating hormone; GnRH, gonadotropin-releasing hormone; LH, luteinizing
hormone.
the loss of normal LH pulses from the anterior pitui-
tary.43 LH and FSH levels remain increased, alongside
serum GnRH. The hallmark of CKD is reduced testoster-
one levels that result in impaired stimulation of the Ser-
toli cells and a consequential decrease in
spermatogenesis.44 In addition, males with CKD have
significantly reduced serum levels of AMH compared
with their healthy counterparts, which already is appar-
ent at early stages of disease but more prominent in late
stages, and appears to play a role in the impairment of
effective spermatogenesis.38,45 Finally, high levels of
PRL also are evident in males with CKD, secondary to
both reduced kidney clearance and increased production,
similar to females.9 Furthermore, common factors
among males with advanced CKD, including hyperpara-
thyroidism and zinc deficiency, also may contribute to
hyperprolactinemia.23 High PRL levels result in suppres-
sion of gonadotropin release, and further inhibition of
testosterone production.5
Akin to the potential for reversibility of the hypothala-
mus−pituitary−ovarian axis disruption in females,
improvement in the male sex hormone milieu has been
described with intensive dialysis or successful kidney
transplantation. A small observational study followed up
30 males as they transitioned from conventional to
145
intensive hemodialysis, and reported a significant
decrease in PRL levels and an increase in testosterone
levels, while LH and FSH levels remained unchanged.23
Similarly, although most studies are performed in small
cohorts, a significant increase in testosterone, and reduc-
tions in PRL, LH, and FSH, have been described after
transplantation.46 A prospective study of 12 men who
were followed up for 12 months after kidney transplanta-
tion reported a rapid reduction of PRL and LH to normal
levels after transplantation, although FSH levels actually
increased.47 Furthermore, a nonsignificant trend toward
increased AMH levels and serum testosterone was
shown, although this observation was in the context of
preoperative testosterone levels already being in the nor-
mal range. This highlights the potential for a more rapid
recovery of Leydig cell function, compared with Sertoli
cell function, after kidney transplantation.
Male Testicular Function
Parallel to the sex hormone derangement shown in males
with CKD, there is consequential impairment of sper-
matogenesis in this population.39,44,45 Requiring high
levels of testosterone secreted from the Leydig cells of
the testis, spermatogenesis is closely regulated by Sertoli
146
cells, which provide metabolic and structural support to
developing sperm cells. A study by Zachoval et al39
assessing semen quantity and quality of 74 males with
dialysis-dependent CKD, reported that males with CKD
had significantly lower volumes of ejaculate, and
decreased sperm count and concentration compared with
healthy controls. Furthermore, the semen analysis in the
CKD group showed comparatively reduced sperm motil-
ity and an increase in abnormal sperm morphology. Sub-
sequent studies in the broader CKD population have
recorded similar results, highlighting that compared with
healthy individuals, males with CKD have a reduction in
sperm count and concentration, as well as reduced sperm
motility, that appears to be linked to the severity of
CKD.44,45
Gender Considerations in Sex Hormones and CKD
Although a discussion on the fascinating interplay
between body and mind is beyond the scope of this
review, it may be worth mentioning that a series of stud-
ies tried to better understand the influence of depression
and chronic stress on sex hormones, although no studies
specifically included individuals living with CKD.48,49
The interplay is probably very complex, and some inves-
tigators have suggested that the effect of chronic stress
and depression is different in men and women, being
more relevant in the latter.49 There is limited knowledge
on the interplay between gender, gender-related stress,
and sex hormones, an important area warranting future
exploration in a population at high prevalence of depres-
sion and chronic stress, such as those with CKD.
SEXUAL FUNCTION AND CKD
Sexual dysfunction is broadly defined as disorders of
sexual desire, arousal, orgasm, or sexual pain that results
in reduced sexual satisfaction.50
Female Sexual Function
The prevalence of sexual dysfunction in females with
CKD is high, although, unlike the pattern in males, it
does not appear strictly related to the degree of kidney
dysfunction.51,52 According to a recent meta-analysis
that included 47 studies with 3,490 women living with
CKD and treated with dialysis or transplantation, with a
relatively low median age (45.2 y), the overall preva-
lence of sexual dysfunction was 74%, with relatively
wide 95% confidence intervals (CI) of 67% to 80%.51 A
lower prevalence of sexual dysfunction was reported in
individuals treated with a kidney transplant (63%), an
intermediate prevalence in peritoneal dialysis, and the
highest prevalence in individuals treated with hemodial-
ysis (80%). As in the overall population, older age and
S.M. Dumanski, D. Eckersten, and G.B. Piccoli
menopause were associated with a higher prevalence of
sexual dysfunction.
Other studies have focused on the prevalence of sex-
ual activity in women with CKD treated with dialysis,
and have reported that more than 80% of women on
hemodialysis were not sexually active, with the primary
reasons described in order as follows: lack of interest
(>40%) and lack of a partner (39%).53 In a large survey
of more than 600 women with CKD treated with hemodi-
alysis, although more than half lived with a partner, only
35% reported being sexually active.54 Furthermore, of
the overall study sample, 84% reported some degree of
sexual dysfunction.
Sexual dysfunction in females with CKD may be
related to a variety of factors, including reduced sexual
desire, impaired vaginal lubrication, difficulties achiev-
ing orgasm, or dyspareunia.55 Hypoestrogenemia may be
a causative factor of female sexual dysfunction in CKD,
specifically related to impaired vaginal lubrication, and
transdermal administration of estrogen has been linked
to improved sexual function in this population.56
Increased PRL levels may be associated with reduced
sexual desire in females living with CKD, but it is
not clear whether treatment with bromocriptine is
beneficial.57
Some studies have reported decreased rates of female
sexual dysfunction after kidney transplantation com-
pared with those with predialysis and dialysis-dependent
CKD; similar to the rates reported in the general popula-
tion.52 Furthermore, a prospective study that followed up
39 females from dialysis-dependent CKD through suc-
cessful kidney transplantation reported a significant
increase in sexual activity after kidney transplantation.31
In contrast, a large meta-analysis suggested that the prev-
alence was consistently higher in the kidney transplant
population than in the general population.51 With the
limits of high heterogeneity in the study, the meta-analy-
sis quantified a dramatically high prevalence of sexual
dysfunction symptoms that are well known to negatively
affect the quality of life, and underlines how much more
knowledge is needed to manage this undertreated clinical
entity in females with CKD.
Male Sexual Function
Self-reported sexual dysfunction has been recorded in
up to 80% of males with CKD, although prevalence
ranges widely.43,58 Rates of sexual dysfunction in
males with CKD are higher compared with healthy
controls, and, in the very few comparative studies
available, prevalence also was higher than that
recorded in other chronic illnesses that share common
sociocultural barriers, thus suggesting that the high
prevalence found in CKD is the result of physical as
well as social and psychological issues inherent to
kidney dysfunction.59,60 In keeping with the important
Reproductive Health in CKD
role of physical alterations, sexual dysfunction in
males is tightly linked with the degree of kidney
function impairment.5 Sexual dysfunction in males
with CKD may be related to reduced sexual desire,
erectile dysfunction, difficulties achieving orgasm, or
abnormal ejaculation.
Hypogonadism may contribute to sexual dysfunction
in males, specifically as it relates to reduced sexual
desire,9 but the efficacy and safety of testosterone ther-
apy in the CKD population is not clear.5 Elevated PRL
in males with CKD is associated with erectile dysfunc-
tion,9 although treatment of erectile dysfunction in indi-
viduals living with CKD with bromocriptine has shown
mixed results.57 The most rigorously studied treatment
for erectile dysfunction in males with CKD is phosphodi-
esterase-5 inhibitor administration, which consistently
shows significant improvement in erectile function com-
pared with placebo.9
The most well-studied aspect of sexual dysfunction in
males with CKD is erectile dysfunction (ED), estimated
as present in approximately 10% of the general male
population,61 and, according to a recent meta-analysis of
more than 7,000 males with kidney failure, found with
high prevalence (71%) in the CKD population.62 The
prevalence of ED was lower (59%) among kidney trans-
plant recipients, highest (82%) in individuals with CKD
starting dialysis, and was similar in peritoneal dialysis
(71%) and hemodialysis (79%). Differences in case mix
and comorbidity may explain most of the differences
between dialysis types, while the decrease in prevalence
between individuals initiating dialysis and individuals
treated with established dialysis or kidney transplanta-
tion supports once more the importance of the overall
metabolic control.
Although kidney transplantation has been associated
with an improvement in sexual function compared with
individuals with dialysis-dependent CKD, the prevalence
of ED after kidney transplantation appears to be higher
than in the general population.9,63,64 This pattern was
confirmed in a meta-analysis that included 20 studies
and more than 1,600 kidney transplant recipients.65 The
study, highlighting the heterogeneity of the data, did not
allow firm confirmation of the positive effect of kidney
transplantation, in particular in patients with severe ED.
The meta-analysis points out the poor quality of many
studies and suggests that nonmetabolic factors, namely
severe vascular or neuropathic impairment, may explain
the lack of reversibility of the most severe forms.
Gender Considerations in Sexual Function and CKD
Although sex-related factors contribute to the experience
of sexual dysfunction in females and males with CKD, a
number of gender-related factors have a strong influence
on sexual health in this population (Table 1).
147
Table 1. Gender-Related Factors Contributing to Sexual Health
in Chronic Kidney Disease
Availability of social networks
Difficulties finding an intimate partner(s)
Rejection experiences by potential intimate partner(s)
Negative perception of body image
Experience of anxiety or depression disorders
Reduced adherence to treatment
A gendered experience exists between men and
women with CKD with respect to finding an intimate or
sexual partner. A qualitative study of 40 young adults
with CKD treated with dialysis or kidney transplant
showed that men have increased difficulty, compared
with women, discussing their kidney disease with poten-
tial partners.66 Men consistently reported previous expe-
rience with rejection by potential intimate partners, and
worried about the timing of disclosure of their CKD and
associated treatments. In addition, men reported fewer
social networks than women, which is important in find-
ing intimate partnerships, and were more likely to look
for partners on the internet to avoid face-to-face rejec-
tion. This difference in intimate partner-seeking behavior
has the potential to influence the sexual activity and sex-
ual satisfaction in women and men with CKD, which are
important components of overall sexual health.
An individual’s body image likewise is very impor-
tant in overall sexual health.9,43 Body image concerns
specific to people living with CKD may include dialysis-
related features such as fistulas and dialysis catheters or
dialysis equipment in the bedroom, transplant-related
features such as scars from surgeries or immunosuppres-
sion-related weight gain, and/or CKD-related features
such as cessation of urination or edema. An interesting
study reported that women have a more negative body
image perception, especially as it relates to sexual activ-
ity, and are more dissatisfied with their physical appear-
ance as compared with men.67 Body image can have a
notable effect on sexual function in both men and
women with CKD,66 but the recognition of the dispro-
portionate effect on women needs to be recognized to
optimize sexual function assessment and management in
this population.
CKD is associated with a high prevalence of depres-
sion and anxiety disorders, both of which can have an
important impact on sexual health.68,69 A study of more
than 100 people with CKD treated with dialysis reported
a high prevalence of sexual inactivity, sexual dissatisfac-
tion, and depression, alongside low quality of life.69 In
this study, low quality of sexual life was predicted by
anxiety in men, but by depression in women, highlight-
ing important gender differences.
Gender may contribute to treatment adherence, but
evidence is conflicting, with some studies reporting
superior adherence in men,70 and some in women.71 In a
cross-sectional analysis of adherence to antihypertensive
148
medications according to gender, Holt et al72 reported an
association with poor sexual functioning in men only,
possibly related to the presence (or fear of) drug-related
effects on sexual health. This link between poor sexual
function and reduced adherence has important implica-
tions in the CKD population, with high rates of antihy-
pertensive use. In men with CKD, poor adherence to
antihypertensive medications has the potential to further
impair vascular dysfunction, which paradoxically can
result in worsening of ED.9
FERTILITY AND CKD
Although approximately 10% of all couples worldwide
experience infertility, defined as the failure to establish
pregnancy after 1 year or more of regular unprotected
sexual intercourse,73 infertility is more common in indi-
viduals with CKD, compared with the general
population.3
Female Fertility
An early observational study by Cochrane and Regan15
that completed gynecologic assessment of females with
dialysis-dependent CKD reported a prevalence of infertil-
ity in this population of 92%. Specifically, of 24 female
participants with the potential for pregnancy (reporting
menstruation and regular sexual activity, but not using
contraception), 22 met the criteria for infertility. However,
the large-scale prevalence of infertility in the CKD popu-
lation has been difficult to ascertain, largely owing to
inadequate or absent screening and documentation of
CKD in studies on infertility, and to the limited number
of studies of these issues in the CKD population, espe-
cially in individuals not treated with kidney replacement
therapy. Furthermore, most dialysis and transplantation
registries do not gather information on conception and
birth rate. However, because the dialysis and transplant
CKD populations are more easily traced and character-
ized, more information is available on patients treated
with kidney replacement therapy, and these data are the
basis for inferring the fertility rate in CKD patients.
One of the most important sources of data is the Aus-
tralia and New Zealand Registry of Dialysis and Trans-
plantation (ANZDATA), which also provides periodic
updates, thus allowing analysis of changes over time.
Interestingly, studies from ANZDATA in the first decade
of the new millennium suggested a marked reduction of
fertility on dialysis, with an almost 1:10:100 gradient of
probability of a live-born baby between females on dial-
ysis, with a functioning kidney graft, and the general
population.74 This observation was in line with a nation-
wide study in Italy using systematic telephone interviews
of female patients with dialysis-dependent CKD and kid-
ney transplantation registry data,19 as well as registry
data in the United Kingdom for the same period.75,76
S.M. Dumanski, D. Eckersten, and G.B. Piccoli
However, a recent report from the ANZDATA
highlighted that, compared with the general population
(61.9 live births/1,000 women/y), there is an overall sta-
ble fertility rate in the kidney transplant population (21.4
live births/1,000 women/y), but a marked increase in
pregnancies in the female dialysis population (5.8 live
births/1000 women/y), perhaps indicating a cultural shift
toward permissive attitudes about pregnancy in females
treated with dialysis.77 Similarly, a recent study from the
United States reported a pregnancy rate of 17.8 per
1,000 person-years in females with CKD treated with
dialysis (however, only in one third of cases was a live-
born baby recorded, the others were divided almost
evenly between loss to follow-up evaluation and preg-
nancy loss).78 In both studies, ethnicity played a major,
albeit divergent, role, because in Australia the birth rate
was higher in white women, while in the United States
the pregnancy rate was significantly higher in ethnic
minorities.
With recognition that a multitude of factors have the
potential to contribute to the low pregnancy and live-
birth rates in the CKD population, it is likely that infertil-
ity has a considerable effect. We were unable to locate
any studies that specifically examined the prevalence of
infertility in CKD, outside of the kidney transplant and
dialysis-dependent CKD populations, but it is reasonable
to postulate that infertility rates related to hypothalamic
−pituitary−gonadal axis dysfunction increase alongside
the severity of kidney dysfunction.8,79,80
Intensive hemodialysis has been linked to an improve-
ment in female fertility, and even in the absence of large-
scale evidence, some investigators have suggested, on the
basis of small but well-studied series, that intensive hemo-
dialysis may favor conception.81,82 A small cohort study
from Canada reported a conception rate of approximately
15% in females with dialysis-dependent CKD treated with
intensive dialysis,82 which is higher than previously pub-
lished conception rates. Furthermore, a systematic review
addressing the relationship between dialysis intensity
(hours per week and sessions per week) and pregnancy
outcomes, reported a trend toward improved pregnancy
outcomes with more intensive dialysis schedules.83
Kidney transplantation also has been associated with
improved fertility outcomes in females, implied by the
10-fold increase in pregnancy rates in this population
compared with those with dialysis-dependent CKD.19,74
After successful kidney transplantation in females,
increased rates of normal menstruation and ovulatory
cycles have been reported in multiple studies,31,36,69 cor-
responding to the improvement or normalization of
female sex hormones.30,31 Although there appears to be
marked improvement in the hypothalamic−pituitary
−ovarian axis and clinical gonadal function in the female
kidney transplant population, it remains unclear why the
pregnancy rate in this population remains 10-fold lower
than in the general population.3,19,76
Reproductive Health in CKD
Male Fertility
Even less is known about male fertility in CKD and,
once more, more data are available in males with CKD
treated with kidney transplantation. Although the hypo-
thalamic−pituitary−testicular axis appears to be
impacted positively by successful kidney transplantation,
improvement in resultant testicular function and sper-
matogenesis remains unclear. An early prospective study
of 30 males undergoing kidney transplantation reported
an improvement in sperm motility after kidney trans-
plantation, but no improvement in sperm concentration
or morphology was shown.46 More recently, a meta-
analysis of 5 studies reported improved sperm motility
and concentration after kidney transplantation, although
both parameters of semen quality were inferior when
compared with healthy subjects.84 Survey data from 21
transplant centers in France, although reassuring on the
risk of birth defects, reported that compared with the
general population, males with kidney transplantation
had higher rates of male infertility and use of assisted
reproductive technology.85 In keeping with this report, a
recent research letter from the ANZDATA registry,
reporting on a large number of fatherhood events over
40 years, underlined the importance of nonmedical fac-
tors in determining reproductive plans, namely the fear
of malformations resulting from paternal treatments, and
highlighted the importance of reconsidering the delivery
of preconception counseling to improve informed shared
decision making.86
Fertility Treatment
There is a paucity of knowledge surrounding the use of
assisted reproductive technology (ART) in individuals
with CKD. Specifically, it remains unclear whether ART,
especially in the form of in vitro fertilization (IVF), has
similar efficacy in the female CKD population compared
with the general population. It also is unknown whether
IVF carries any additional risk for females with CKD,
which is highly probable, considering the higher baseline
risk of adverse pregnancy-related outcomes.8 Scattered
data and a small case series have suggested that IVF in
females after kidney transplantation is feasible, and that
obstetric outcomes after IVF are comparable with out-
comes in the kidney transplant population with natural
conception, but larger studies are warranted.87-89 Small
studies have examined the use of IVF alongside intracyto-
plasmic sperm injection to achieve pregnancy in partners
of male kidney transplant recipients diagnosed with infer-
tility, and, taken together, these preliminary data indicate
the potential for success, although the results are
mixed.90-92 We were unable to locate any studies that
examined the utility and implications of IVF in the CKD
population before kidney transplantation.
149
Table 2. Gender-Related Factors Contributing to Fertility in
Chronic Kidney Disease
Noninclusive medical definition of infertility
Gendered language in fertility medicine
Infertility stigma against women/females
Gender-based economic inequality
Access to assisted reproductive technology
Gender Considerations in Fertility and CKD
Although sex-specific factors undoubtedly play an
important role in fertility and infertility in CKD, it is
important to recognize that gender-specific considera-
tions are likewise important (Table 2).
Inherent to its medical definition, infertility implies a
sexual relationship between a male and a female, and
thereby is inaccessible to a large proportion of the les-
bian, gay, bisexual, transgender, queer (LGBTQ+) com-
munity.93 A more inclusive terminology, “a person’s
inability to reproduce either as a single individual or
with their partner without medical intervention,”94
including both social infertility (an inability to reproduce
related to factors associated with sexual orientation) as
well as biological infertility (an inability to reproduce
related to factors associated with reproductive function),
has made gains in the legal world,94 but not yet in the
medical community. Awareness and recognition of the
gendered language inherent to discussions about fertility
is an important step in improving access to fertility care
for LGBTQ+ and gender-diverse individuals.
Although women appear to be more receptive to con-
versations about fertility,95 even in straight cis-gendered
couples, the gendered language used in fertility medicine
can augment the infertility stigma against women, per-
petuating a perception of failure and inadequacy, as
opposed to recognizing the potential for male-factor or
shared infertility.96
Gender-based economic inequality is widespread and
women are more likely to have a lower income and less
opportunity to participate in household financial deci-
sions.97 This may be compounded in women living with
CKD, a disease associated with a high economic bur-
den.98 This can have several implications, including
access to ART, often requiring significant out-of-pocket
expenses, as shown by a recent study that reported more
than half of couples pursuing ART will spend all of their
savings on treatment, and consider taking on additional
jobs or borrowing money from loved ones.95 The eco-
nomic burden related to ART should be discussed openly
with the health care team.
CONCLUSIONS
Reproductive health disturbances in CKD are common,
and are identified by people living with CKD as research
150
and health priorities. Both physical and psychosocial
components of reproductive health are affected by CKD,
highlighting the impact of both sex and gender in this
important area of health. An active awareness by neph-
rologists of the sex and gender implications inherent to
reproductive health and complications in people living
with CKD is needed to optimize strategies for reproduc-
tive health assessment and management.
ACKNOWLEDGMENTS
We thank Ms Hayley Duff for graphic design.
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