Improved progesterone levels and pregnancy following vitex agnus-castus (Chaste tree) supplementation in a case of recurrent pregnancy loss: A case report

Abstract

Recurrent pregnancy loss (RPL) occurs in 1% of couples and is defined as three consecutive failed pregnancies. While controversial, evidence exists that adequate levels of progesterone may be an important factor in pregnancy maintenance and that increasing levels of progesterone may increase the likelihood of success. Vitex agnus castus (chaste tree) is a herbal medicine with evidence to support its use in a variety of hormonal conditions, including premenstrual disorder and cyclic mastalgia through modulation of reproductive hormones. This report details a case of RPL in which low progesterone levels were observed. One month of supplementation with Vitex was followed by successful pregnancy with normal levels of serum progesterone and a live birth at full term. A second successful pregnancy followed, also with Vitex supplementation. Although the exact role of Vitex in this case cannot be confirmed, it adds evidence to the hypothesis that this herb may be an effective intervention in cases of RPL, particularly those involving low progesterone, and that more research is warranted.

Full text

Australian Journal of Herbal and Naturopathic Medicine 2018 30(3)
122 © NHAA 2018
Monique Aucoin BMSc, ND and Ashley Weber ND
Canadian College of Naturopathic Medicine, Toronto, Ontario, Canada
Contact information
Monique Aucoin, Research Fellow, Canadian College of Naturopathic Medicine
Email: maucoin@ccnm.edu
Improved progesterone levels and pregnancy
following Vitex agnus-castus (chaste tree)
supplementation in a case of recurrent pregnancy
loss: A case report
Abstract
Recurrent pregnancy loss (RPL) occurs in 1% of couples and is defined as three consecutive failed pregnancies. While controversial,
evidence exists that adequate levels of progesterone may be an important factor in pregnancy maintenance and that increasing
levels of progesterone may increase the likelihood of success. Vitex agnus-castus (chaste tree) is a herbal medicine with evidence
to support its use in a variety of hormonal conditions, including premenstrual disorder and cyclic mastalgia through modulation
of reproductive hormones. This report details a case of RPL in which low progesterone levels were observed. One month of
supplementation with Vitex was followed by successful pregnancy with normal levels of serum progesterone and a live birth at full
term. A second successful pregnancy followed, also with Vitex supplementation. Although the exact role of Vitex in this case cannot
be confirmed, it adds evidence to the hypothesis that this herb may be an effective intervention in cases of RPL, particularly those
involving low progesterone, and that more research is warranted.
Keywords: Vitex agnus-castus, herbal medicine, progesterone, spontaneous abortion, recurrent pregnancy loss, luteal phase
defect.
Introduction
Recurrent pregnancy loss (RPL) has various
denitions, making clinical research and diagnosis
challenging. For the purposes of this case study, we
dene recurrent pregnancy loss as at least 3 consecutive
failed pregnancies at any time prior to 20 weeks post-
menstruation. Pregnancy loss is relatively common and
estimated at 15–20% of pregnancies, with the majority
occurring prior to 10 weeks1, while RPL, as dened
above, occurs in approximately 1% of couples2.
Possible causes and contributing factors of RPL
include chromosomal abnormalities, thrombophilic
disorders such as antiphospholipid syndrome, uterine
malformations, infections, hormonal and metabolic
dysfunctions such as diabetes mellitus, and sperm DNA
fragmentation1,2. Low progesterone and luteal phase
defect may also play a role3. Possible lifestyle factors may
include, smoking, obesity and use of alcohol, caffeine or
social drugs including cocaine1. Other case characteristics
associated with RPL may include psychological factors,
unmanaged hypothyroidism and diabetes1. At least half
of RPL cases have no identiable cause, and it is thought
that these cases, as well as most cases of RPL, have
multiple contributing factors1.
Conventional treatment of RPL aims to investigate the
cause and initiate appropriate treatment. This may include
surgical considerations, anticoagulants or progesterone
administration. In couples without an identiable cause,
psychological support pre-conception and in early
pregnancy has shown signicant benet4,5.
Progesterone
Progesterone is a hormone secreted by the corpus
luteum post-ovulation and develops the secretory
endometrium in preparation for embryo implantation.
If implantation occurs, the corpus luteum continues to
produce progesterone until weeks 8–10 gestation when
the placenta takes over6. Progesterone is essential for
pregnancy initiation and maintenance. It promotes
maternal immune tolerance to the foetus and mitigates
uterine contractility7. It also triggers the production of
progesterone induced blocking factor (PIBF) which
possesses anti-abortive effects in vivo7. Several studies
show an association between lower levels of serum
progesterone and PIBF and higher risk of spontaneous
abortion (SA)7. Insufcient progesterone secreted by
the corpus luteum may be associated with what is
Research

Australian Journal of Herbal and Naturopathic Medicine 2018 30(3)
123© NHAA 2018
referred to as a luteal phase defect. Luteal phase defect
or deciency is dened as “insufcient progesterone
exposure to maintain a normal secretory endometrium
and allow for normal embryo implantation and growth”8.
Clinically, this may present as a shortened luteal phase
and an overall shortened menstrual cycle9, and primary
infertility or recurrent pregnancy loss in rst trimester10.
Assessment of risk for RPL has been based on combined
progesterone levels, luteal phase length, and histological
features of the endometrium9. Luteal phase defect has
been controversial due to inconsistencies in the evidence
base for diagnosis and treatment. Findings from research
have shown that women with RPL are at signicant risk
for lower progesterone levels in the luteal phase, with
40% of women having luteal phase defect10,11.
Causes of low progesterone are unclear; however,
it has been suggested that latent hyperprolactinaemia
(pre-menstrual or stress-induced elevated levels of
prolactin) may inhibit corpus luteum development and
therefore subsequent progesterone release12. Other
possible associations include psychological perceived
stress13, excessive exercise14 and exposure to endocrine-
disrupting chemicals15.
Pharmacological preparations of progesterone
such as progestogen have not been shown to benet
pregnancy in the general population; however, a
statistically signicant decrease in SA in women with
RPL has been documented16. Additionally, progestogen
has been shown to reduce the rate of SA when used
in women with threatened miscarriage17. While use
of exogenous progesterone is common, especially in
assisted reproductive technology, concerns exist that
intrauterine exposure to exogenous progesterone may
increase risk of genital abnormalities in the fetus, such
as hypospadias16.
Vitex agnus-castus
Introduction and biochemistry
Vitex agnus-castus, commonly known as chaste
tree, is a deciduous plant with purple-black berries
native to Europe and Central Asian countries that is
used in botanical medicine18. Active constituents of
Vitex include avonoids, diterpenes and glycosides, all
of which may exert a hormonal action. In vitro studies
show dopaminergic activity, resulting in prolactin
inhibition. As previously discussed, elevated prolactin
in humans may inhibit ovulation, development of the
corpus luteum and sufcient progesterone secretion and,
therefore, inhibition of excessive prolactin inhibition
may subsequently increase progesterone12. Additionally,
Vitex’s action of lowering prolactin levels by way of
dopaminergic activity also affects follicle stimulating
hormone (FSH), and oestrogen and testosterone in
women and men, respectively19. Oestrogenic activity is
also exerted by linoleic acid found in the fruit of Vitex19.
Animal studies have shown increased progesterone levels
with Vitex supplementation20.
Uses
Vitex is often used for female reproductive disorders,
with the majority of the research focusing on premenstrual
syndrome (PMS) and premenstrual dysmorphic disorder
(PMDD). Numerous studies have shown signicant
benet in PMS and PMDD, despite lack of consistency
in preparations of Vitex19,21-24. Hyperprolactinaemia may
be an important factor in these conditions. As previously
discussed, elevated prolactin may inhibit progesterone
secretion12. Vitex’s documented actions of lowering
prolactin levels may, in turn, remove its inhibitory effect
on progesterone, ultimately normalising progesterone and
contributing to positive benets in PMS and PMDD19,25.
Additionally, due to prolactin inhibition, Vitex has
been shown to improve latent hyperprolactinaemia and
cyclic mastalgia12. Other research has shown benets in
menopause and fracture healing, and Vitex possessing
antimicrobial and antioxidant activity26.
Positive results on menstrual cycle defects have
also been shown for use of Vitex agnus-castus. One
study involving women with luteal phase defects due
to latent hyperprolactinaemia found progesterone levels
normalised and luteal phase lengthened after 3 months
of supplementation with Vitex27. FertilityBlend, a
proprietary blend of herbs and vitamins, with Vitex as
a key component, found a signicant increase in luteal
progesterone levels as well as pregnancy rates in a group
taking the supplement for three months28. However, due
to the proprietary blend of multiple ingredients, outcomes
cannot be attributed to Vitex alone. While Vitex has well-
documented hormonal activity, which may theoretically
inuence fertility, we have found no research directly
testing the use of Vitex agnus-castus for low progesterone
in RPL, with primary outcome of maintained pregnancy
to second trimester.
Case presentation
Presenting concern
AB, a Caucasian woman presented at age 29 with
concerns of recurrent pregnancy loss (RPL). She reported
a history of four chemical pregnancies detected by urine
or serum bHCG, three of which were in the preceding
eight months. These pregnancies resulted in complete
spontaneous abortion (SA) at ve weeks’ gestation
without intervention.
Laboratory assessment was completed immediately
prior to and during the fourth SA. At 5 weeks plus 2 days’
gestation, bHCG was 459 IU/ml (normal range: 18–7340
IU/ml) and progesterone was 22.1 nm/L (1st trimester
normal range: 18–150 nm/L). At 5 weeks plus 4 days,
bHCG was 374 IU/ml and SA occurred two days later.
Past medical history
AB reported a history of moderate facial acne vulgaris
and moderate primary dysmenorrhea since menarche.
Bilateral dermoid ovarian cysts approximately 1 cm by
2 cm in size were an incidental nding on ultrasound
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Australian Journal of Herbal and Naturopathic Medicine 2018 30(3)
124 © NHAA 2018
four years prior. They were monitored annually by
ultrasound with no signicant change. She had no history
of abnormal Papanicolaou tests. AB reported no family
history of infertility or genetic conditions. The patient’s
partner reported no past or current medical concerns and
no family history of infertility or genetic conditions.
Psychosocial history
The patient lives with her husband and reports
moderate work stress, which she manages with
mindfulness meditation.
Medication
AB was not taking any prescription or over-the-
counter medication. She used topical benzole peroxide
for management of acne vulgaris. She was supplementing
folic acid (methylfolate 1000 mcg per day).
Diagnostic focus and assessment
Other laboratory assessment included TSH 0.87
mIU/L (0.3–5.0 mIU/L). Physical examination was
within normal limits.
Therapeutic approach
A prescription was made for Vitex agnus-castus herbal
supplement at a dose of 166.6 mg of 6:1 fruit extract from
1000 mg of fruit per day (Brand: Mediherb, 2 capsules
per day). AB reported a high level of compliance and no
adverse reactions.
Follow-up and outcomes
After one month of supplementation, the patient
completed a home pregnancy test, which was positive.
Laboratory assessment completed at 5 weeks plus 2 days’
gestation revealed bHCG of 1200 IU/ml and progesterone
of 85 nm/L (Table 1). Ultrasound examination two days
later revealed a singleton uterine pregnancy.
This laboratory and imaging assessment took place
with an obstetrician/gynaecologist, who completed a
fellowship in reproductive endocrinology and infertility,
and to whom AB was referred by her primary health
care provider. The positive home pregnancy test
preceded the initial visit with this clinician and, thus,
no other investigations related to causes of infertility
were completed. The specialist advised the patient to
discontinue the herbal supplement at 5 weeks plus 4 days
and prescribed vaginal pessaries of progesterone (200mg
twice per day) until 10 weeks’ gestation.
Subsequent ultrasounds and screening testing were
normal and the patient had a healthy pregnancy, resulting
in spontaneous vaginal delivery of a healthy infant at full
term.
When the patient was 15 months’ postpartum, she
restarted the Vitex formula. One month later she conceived
naturally. The Vitex formula was continued until 8 weeks’
gestation and then discontinued. Discontinuation at 8
weeks was based on the placenta assuming the role of
progesterone production from the corpus luteum at this
point in pregnancy and the patient’s desire to discontinue
intervention at the earliest opportunity. At the time of
writing, the patient is 38 weeks’ pregnant. Ultrasound
assessment at 12, 20 and 28 weeks gestation revealed a
healthy, singleton, uterine pregnancy.
Discussion
The precise role that supplementation with Vitex
played in this case is unclear; however, repeated blood
work and a proposed biological mechanism lend
support to the hypothesis that the intervention may raise
progesterone levels or normalise another physiologic
parameter, resulting in maintenance of the pregnancy.
Proposed mechanism
In this case, progesterone levels improved
between subsequent pregnancies following Vitex
supplementation, and pregnancy was subsequently
maintained. Adequate progesterone production by the
corpus luteum is known to play an important role in
the maintenance of pregnancy through the rst eight
weeks of gestation through a variety of mechanisms.
As discussed, Vitex may increase progesterone levels
by way of inhibiting prolactin. Prolactin levels were not
measured in this case; therefore the role of prolactin is
unclear. Documented uses of Vitex supports the proposed
mechanism of action of increasing progesterone levels
leading to maintained pregnancy.
Strengths and limitations
A strength of this case report is that the laboratory
testing was completed at the same gestational age for two
consecutive pregnancies, allowing for comparison prior
to and after Vitex supplementation.
This report has limitations. Progesterone levels were
not assessed in the earlier pregnancies, so it is unclear
if low progesterone was associated with previous SAs.
Although it may be suspected, this cannot be conrmed.
Unfortunately, prolactin levels were not assessed in this
case, which also limits the ability to draw inferences
about the therapeutic mechanisms.
Table 1: Laboratory values for AB at 5 weeks plus 2 days gestation
Reference range 4th pregnancy with no intervention 5th pregnancy with Vitex supplementation
bHCG 18–7340 IU/ml 459 IU/ml 1200 IU/ml
Progesterone 18–150 nm/L 22.1 nm/L 85.0 nm/L
Outcome Spontaneous abortion at 5 weeks +6
days
Pregnancy maintained with full-term live birth
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Australian Journal of Herbal and Naturopathic Medicine 2018 30(3)
125© NHAA 2018
Safety
The safety prole of Vitex is well established and
adverse events have been shown to be infrequent, mild and
reversible. Despite acknowledgement that Vitex may have a
therapeutic role29, use in pregnancy and lactation is currently
not recommended based on lack of safety evidence30.
Further research
Few therapeutic options are available for women
experiencing RPL in the absence of an identiable cause.
While therapeutic progesterone is a valuable tool, some
concerns about side effects to the developing foetus have
been cited or hypothesised16. The potential for Vitex
to play a role in the maintenance of hormonal balance
in early pregnancy and prevention of SA would be a
valuable therapeutic tool. This case report highlights a
need for further research on this topic in order to elucidate
the effect of Vitex on hormonal balance, progesterone
and prolactin in particular, and the role that the herb may
play as an intervention in cases of RPL. Randomised
controlled trials investigating Vitex supplementation in
women with RPL are needed to further explain its clinical
effectiveness for progesterone augmentation, prevention
of SA and safety in pregnancy.
Conclusion
This report details a case of two successful pregnancies
following RPL with Vitex agnus-castus supplementation.
Vitex may be useful in the prevention of recurrent SA
related to sub-optimal progesterone. More research,
including intervention studies, is needed to fully
investigate the potential for efcacy and safety.
Acknowledgement
Joy Dertinger for assistance in manuscript preparation.
Permission
The patient provided written consent for publication
of this report. We thank her for participating.
Conflict of interest
The authors declare no conicts of interest.
Funding
No funding was provided for this case report.
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