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Oral Allylestrenol: A Pregnancy-supporting Progestogen

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Allylestrenol is a synthetic progestogen that has been in therapeutic use in the management of mild to severe cases of certain obstetric complications, like selected forms of miscarriage/abortion, threatened preterm labor, intrauterine growth restriction (IUGR), and gestational hypertension. Natural progesterone may be used for treatment; however, it has the property of being rapidly metabolized in the liver besides having little or no oral activity. While there are many other synthetic and orally administrable progesterone analogs in the market, most of them, which are 19-nortestosterone derivatives, possess various undesirable side effects like symptoms of intolerance and a tendency to virilization. Allylestrenol, despite being a 19-nortestosterone derivative, has no known side effects including those attributed to the other members of its class, which is theorized to be due to subtle differences in its chemical structure, giving it a unique mechanism of action consisting of a triple effect—trophoblastic, placentotropic, and β 2 -adrenergic. The present review is mainly aimed at understanding the whys and wherefores behind the molecule's moderate efficacy and remarkable safety along with examining the data from various studies. How to cite this article Malhotra N, Garg R, Malhotra N, Malhotra J. Oral Allylestrenol: A Pregnancy-supporting Progestogen. J South Asian Feder Obst Gynae 2017;9(4):297-303.
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Oral Allylestrenol: A Pregnancy-supporting Progestogen
Journal of South Asian Federation of Obstetrics and Gynaecology, October-December 2017;9(4):297-303 297
JSAFOG
ABSTRACT
Allylestrenol is a synthetic progestogen that has been in thera-
peutic use in the management of mild to severe cases of certain
obstetric complications, like selected forms of miscarriage/abor-
tion, threatened preterm labor, intrauterine growth restriction
(IUGR), and gestational hypertension. Natural progesterone
may be used for treatment; however, it has the property of being
rapidly metabolized in the liver besides having little or no oral
activity. While there are many other synthetic and orally adminis-
trable progesterone analogs in the market, most of them, which
are 19-nortestosterone derivatives, possess various undesir-
able side effects like symptoms of intolerance and a tendency
to virilization. Allylestrenol, despite being a 19-nortestosterone
derivative, has no known side effects including those attributed
to the other members of its class, which is theorized to be due
to subtle differences in its chemical structure, giving it a unique
mechanism of action consisting of a triple effect—trophoblastic,
placentotropic, and β2-adrenergic. The present review is mainly
aimed at understanding the whys and wherefores behind the
molecule’s moderate efcacy and remarkable safety along with
examining the data from various studies.
Keywords: Allylestrenol, Pregnancy, Progestogen.
How to cite this article: Malhotra N, Garg R, Malhotra N,
Malhotra J. Oral Allylestrenol: A Pregnancy-supporting Pro-
gestogen. J South Asian Feder Obst Gynae 2017;9(4):297-303.
Source of support: Nil
Conict of interest: None
Date of received: 10 October 2017
Date of acceptance: 1 December 2017
Date of publication: January 2018
INTRODUCTION
Progestogens can be classified as natural or synthetic.1,2
Natural compounds are those with chemical structures
similar to those produced by living organisms. In contrast,
synthetic progestogens (or progestins) are compounds gen-
erated in the laboratory whose structures have been modi-
fied and do not correspond to a naturally occurring steroid.
Progesterone plays a crucial role in the maintenance
of pregnancy. Natural micronized progesterone is
approved and available in India.3 Natural progesterone
has mixed results when used in the first trimester in
pregnant women with a history of recurrent miscarriage.
Progesterone has been widely used to prevent threatened
miscarriage, recurrent miscarriage, and preterm labor.
In a Cochrane review,4 a meta-analysis performed on six
randomized trials including singleton pregnancies with
previous preterm birth, progesterone supplementation
was associated with a significant reduction of delivery
before 32 weeks and of perinatal mortality.
In a large meta-analysis5 consisting of 14 rando mized,
controlled trials (2,158 women selected regardless of
gravidity and number of previous miscarriages), no sta-
tistically significant difference in the risk of miscarriage
between progestogen and placebo or no treatment groups
was observed. Results from a subsequent double-blind
definitive trial [PROMISE trial, (Table 1)] conducted in
women with a history of recurrent miscarriage,6 and given
vaginal suppositories of micronized progesterone (432
women), progesterone showed no benefit in increasing
the rate of live birth after 24 weeks of gestation. Norman
et al7 conducted a large double-blind, randomized,
placebo-controlled study [OPPTIMUM trial, (Table 1)]
on pregnancy and infant outcomes in women at risk of
preterm birth after being treated with vaginal progester-
one taken daily from 22, 23, or 24 to 34 weeks of gestation.
Progesterone was found to have no significant effect on
the primary obstetric outcome or neonatal outcome or on
the childhood outcome (taking cognitive score as index
of measurement). Progesterone apparently had no long-
term benefit or harm on outcomes in children at 2 years
of age. Another on-going trial is the PRISM (Progesterone
in Spontaneous Miscarriage) trial which is designed to
evaluate the efficacy of vaginal progesterone in women
presenting with vaginal bleeding in the first trimester.
The result of this trial will provide evidence on the use
of progesterone in threatened miscarriage.
The era of Evidence-based Medicine represents inte-
gration of clinical expertise, patient’s values, and best
available evidence in the process of decision-making
related to patient’s health care. The current available
evidence is not in favor of the use of progesterone in
recurrent miscarriage and for prevention of preterm birth.
Thus, there is a need to reexplore the progestogen
molecule especially from synthetic origin which could
provide an effective therapeutic approach in the manage-
ment and prevention of such complications and also at
JSAFOG
EDITORIAL
10.5005/jp-journals-10006-1517
Oral Allylestrenol: A Pregnancy-supporting Progestogen
1Narendra Malhotra, 2Ruchika Garg, 3Neharika Malhotra, 4Jaideep Malhotra
1,3,4Consultant, 2Associate Professor
1,3,4Rainbow IVF, Agra, Uttar Pradesh, India
2Department of Obstetrics and Gynecology, Sarojini Naidu
Medical College, Agra, Uttar Pradesh, India
Corresponding Author: Ruchika Garg, Associate Professor
Department of Obstetrics and Gynecology, Sarojini Naidu Medical
College, Agra, Uttar Pradesh, India, e-mail: ruchikagargagra@
gmail.com
Narendra Malhotra et al
298
the same time should be devoid of adverse effects. Hence,
the present review highlights the detailed evaluation of
allylestrenol, a promising molecule with its pharmacol-
ogy, therapeutic uses, and clinical evidences.
Allylestrenol or allylestrenol or perselin (C21H32O) is
a steroidal small molecule (average molecular weight:
300.48 gm/mol) with progestational activity.8,9 It is widely
marketed throughout Europe, including Russia and many
European countries.9 Allylestrenol is also available in
parts of Asia like Japan, Hong Kong, India, Bangladesh,
Indonesia, and much of Southeast Asia, though notably
not in the United States or Canada.9
Figure 1 shows allylestrenol is a synthetic progestogen
structurally related to progesterone. Allylestrenol is syn-
thesized from norethindrone by treating norethindrone
with ethanedithiol and catalytic boron trifluoride. A thio-
ketal is obtained which is reduced with sodium in liquid
ammonia to result in the desired reductive elimination of
the thioketal together with reduction of the 17-keto group.
Oxidation of this alcohol with chromic acid in acetone
followed by addition of allyl magnesium bromide gives
allylestrenol.10
Earlier, natural progesterone has been used for treat-
ment. However, it had a drawback of being rapidly
metabolized in the liver into its biologically inactive
pregnanediol metabolite besides having little or no oral
activity. Currently, all the progestational agents in thera-
peutic use are synthetic steroids. Progestins have been
recognized by their biological action, instead of their
chemical structure.11
Today, several progestins have become available
which are orally active. These have been products of
19-norandrostenolone and lie somewhere between natural
androgens and estrogens. Although many progestins
have displayed unusually strong progestogenic effects,
various undesirable side effects have also been found, the
two most important being symptoms of intolerance and a
tendency to virilization. Also with several progestogens,
prolonged administration for pregnancy maintenance has
resulted in pseudohermaphroditism in the offspring.12
Allylestrenol, however, seems to be completely free
from androgenic activity as well as well tolerated.12 This
is in agreement with its lack of androgenic activity in
animal studies as well. Allylestrenol in this respect, by
not having any androgenic activity, has no teratological
effects. Allylestrenol is also without estrogenic and gluco-
corticoid activity and treated as a pure oral progestogen.13
MODE OF ACTION
The mechanism of action of allylestrenol is multimodal
and complex as shown in Flow Chart 1.
hCG, human chorionic gonadotropin; hPL, human
placental lactogen; LAP, leucine amino peptidase; CAP,
cysteine aminopeptidase.
Trophoblastic Action
The precursor cells of the human placenta—the tropho-
blasts—first appear 4 days after fertilization as the outer
layer of cells of the blastocyst. The trophoblasts are criti-
cal for a successful pregnancy by mediating such critical
steps as implantation, pregnancy hormone production,
immune protection of the fetus, increase in maternal
vascular blood flow into the placenta, and delivery.
Allylestrenol stimulates the hormonal activity of the exist-
ing syncytiotrophoblast as the latter plays an important
role in producing human chorionic gonadotropin (hCG),
which in turn stimulates the production of progesterone.14
Table 1: Summary of recent clinical trials on the effectiveness of vaginal progesterone therapy
Author Trial name Disease setting Number of patients, arms Drug, dosage Results
Coomarasamy
et al6
PROMISE
(Progesterone
in Recurrent
Miscarriages)
Women with
unexplained
recurrent
miscarriage
n = 836; randomly
assigned to progesterone
(404 women) and
placebo (432 women)
400 mg micronized
progesterone
vaginal
suppositories BID
No signicantly higher
rate of live births with
progesterone therapy
Norman et al7OPPTIMUM (dOes
Progesterone
Prophylaxis To
prevent preterm
labour IMprove
oUtcoMe?)
Women at risk
of preterm birth
n = 1228; randomly
assigned to progesterone
(n = 618) and placebo
(n = 610)
200 mg
progesterone
vaginal
suppositories OD
Progesterone therapy
neither reduced risk of
preterm birth nor composite
neonatal adverse
outcomes, and had no
long-term benet or harm
on outcomes in children at
2 years of age
Fig. 1: Molecular structures of allylestrenol [(17β)-17-(prop-2-en-
1-yl)estr-4-en-17-ol] and natural progesterone (pregn-4-ene-3,20-
dione)
Oral Allylestrenol: A Pregnancy-supporting Progestogen
Journal of South Asian Federation of Obstetrics and Gynaecology, October-December 2017;9(4):297-303 299
JSAFOG
Placentotrophic Action
It was suggested that the pregnancy-maintaining effect of
allylestrenol is at least partly due to a stimulation of the
placental function.14 Progesterone is important to prevent
preterm labor as it reduces the sensitivity of myometrium
to oxytocin;15 and in humans, despite no decrease in
placental progesterone production, activation of similar
pathways preceding labor suggests the presence of an
endogenous antiprogestin, whose secretion from the fetal
adrenal rises markedly at the end of human gestation,16
pregnanediol, human placental lactogen (hPL, also called
human chorionic somatomammotropin), serum heat stable
alkaline phosphatase, serum leucine aminopeptidase, and
oxytocinase.
ß2-Adrenergic Action
Stimulation of the β2-adrenergic receptors has been found
to inhibit uterine contractility. β2-adrenergic receptors are
present in the uterus, whereas the cardiac muscle appears
to contain β1-receptors.17,18
The relatively quick onset of allylestrenol clinical
effect was explained that allylestrenol has some form of
neural-mediated action resulting in uterine relaxation by
stimulating the myometrial β2-receptors. A combination
of actions of allylestrenol—improvement of the tropho-
blastic function, which promotes the production of pro-
gesterone, and the β2-adrenergic action—could account
for the results of this drug in the treatment of myometrial
spasmodic conditions that may interrupt pregnancy.14
Absence of Androgenic Activity
In the study by Bergink et al,13 binding of allylestrenol,
its 3-keto metabolite and reference compounds for the
androgen receptor in MCF-7 cells (human breast tumor
cell line) and for human sex hormone-binding globulin
(SHBG) (an important carrier protein for androgens) is
analyzed. The results are tabulated in Table 2.
At 4°C, the binding of 3-keto-allylestrenol to the
androgen receptor was the same as that of medroxy-
progesterone acetate and about 1.5 times stronger than
Flow Chart 1: Allylestrenol multimodal mechanism of action
Table 2: Relative binding afnity of allylestrenol, its 3-keto metabolite and reference compounds for the androgen receptor in MCF-7
cells and human SHBG
Compound
MCF-7 cells
Human SHBG at 37°CCytosol at 4°C Intact cells at 37°C
Testosterone 32 ± 4* (8) 38 ± 2 (6) 100% (reference)
5α-Dihydrotestosterone 100% (reference) 100% (reference) 446 ± 79 (5)
Allylestrenol 2.8 ± 0.2 (3) <0.2 0.9 ± 0.2 (3)
3-Keto-allylestrenol 29 ± 3 (4) 4.5 ± 1 (3) 2.8 ± 0.2 (3)
Progesterone 5.8 ± 0.7 (3) 0.5 (1) 1 (1)
Norethisterone 17 (1) 7 ± 0.7 (8) 10 ± 0.8 (4)
Medroxyprogesterone acetate 29 ± 2 (3) 8 ± 1.1 (5) 1 (1)
*Mean ± standard error of mean; Number of individual experiments
Narendra Malhotra et al
300
that of norethisterone. At 37°C the binding affinity of
3-keto-allylestrenol was half that of norethisterone and
medroxyprogesterone acetate. 3-Keto-allylestrenol,
allylestrenol, and reference compounds which did not
have androgenic activity (progesterone) displayed 7 to
12 times lower affinities for the androgen receptor in
intact cells than in cytosol whereas compounds with
androgenic activity (testosterone) displayed similar or
slightly lower relative affinity for the androgen receptor
in intact cells than in cytosol. The affinity of allylestrenol
and its 3-keto metabolite for human SHBG was found
to be very low. The natural androgens testosterone and
5α-dihydrotestosterone binds very strongly to SHBG.
Allylestrenol and its 3-keto metabolite bind weakly and
this suggests that androgenic effects due to displacement
of endogenous androgens from SHBG will not occur.
MICRONIZATION
Micronization of progesterone in particle sizes of <10 μm
extensively increases the available surface area of the drug
and enhances the aqueous dissolution rate and intestinal
absorption of progesterone. Similarly, micronization of
allylestrenol also helps in increasing the dissolution rate
and oral bioavailability. Micronization is particularly useful
for poorly water-soluble drugs.19 Allylestrenol, being a
steroid and fat-soluble compound, micronization enhances
its solubility in water and improves the clinical outcome.
Therapeutic Uses and Clinical Evidences
Allylestrenol has proven efficacy and safety in cases of
threatened abortion, recurrent (habitual) abortion, threat-
ened preterm labor, IUGR, or other complications related
to progesterone deficiency.14,20 Allylestrenol has also
been investigated for possible use in men for treatment
of benign prostatic hyperplasia; however, it falls outside
the scope of our present review.
Miscarriage (Threatened and Recurrent
Miscarriage)
Allylestrenol allows for clinical treatment of threatened
abortion as an oral tablet.14,20 Particularly, allylestrenol
treatment during early detection results in a decrease in the
number of miscarriages,14,20 probably due to stimulation
of placental function (Table 3).21
Being a time-tested agent for more than five decades,
allylestrenol was also found to be safe and effective for
use during pregnancy in women with selected cases of
bad obstetric history (recurrent/habitual abortion).
Efficacy of allylestrenol combined with ritodrine (a
tocolytic short-acting β2-adrenoreceptor agonist) was
observed in the treatment of habitual abortion in a much
recent study by JinLan and Lan,22 in 144 patients divided
into two equal groups (observation group, allylestrenol
combined with ritodrine; control group, magnesium
sulfate combined with allylestrenol). The results (Table 4)
showed that efficacy of allylestrenol combined with rito-
drine in the treatment of habitual abortion is significant,
which can improve the rate of pregnancy with no obvious
adverse reactions (Table 5).
Intrauterine Growth Restriction/Fetal Growth
Restriction/Small for Gestational Age
According to one report,23 more than 13.7 million infants
are born every year at term with low birth weight (LBW),
representing 11% of all newborns in developing countries.
This rate is about six times greater than in developed
countries. Almost 75% of all affected infants are born in
Asia (mainly in South-Central Asia), 20% in Africa, and
about 5% in Latin America. The report established that
many developing countries exceeded the internationally
Table 3: Success rate in controlling threatened abortion following
treatment with allylestrenol in some of the studies of various authors
Author
No. of patients
treated with
allylestrenol
Positive
results
Success
rate (%)
Lambillon J 36 33 92
Borglin NE and Eliasson C 99 69 70
Gaudefroy M 27 24 89
Murphy MD and Gindhart
FD*
61 55 90
Despodova C et al 73 68 93
Gyory G et al 54 46 85
Cortes-Prieto J et al 334 244 73
Sen Gupta S 85 74 87
Monasterolo F and
Cassinelli L
444 364 82
*The study published by Murphy MD and Gindhart FD in “The
Journal of the Medical Society of New Jersey” was conducted
in the USA
Table 4: Allylestrenol plus ritodrine vs control (MgSO4 plus allylestrenol) in the treatment of habitual abortion
Observation group Control group
Total effective rate (p < 0.05) 94.44% (68/72) 63.89% (46/72)
Rate of pregnancy (p < 0.05) 77.89% (56/72) 55.56% (40/72)
Progesterone (p < 0.05) (190.12 ± 60.97) mmol/L (163.21 ± 64.88) mmol/L
hCG(p < 0.05) (7,319.98 ± 1,032.03) U/L (5,797.01 ± 954.12) U/L
Adverse reactions Nil Nil
Oral Allylestrenol: A Pregnancy-supporting Progestogen
Journal of South Asian Federation of Obstetrics and Gynaecology, October-December 2017;9(4):297-303 301
JSAFOG
recommended IUGR (>20%) and LBW (>15%) cut-off
levels triggering public health action.
In Japan, Kaneoka et al21 prospectively studied the
effect of allylestrenol treatment on 22 pregnancies with
IUGR cases whose body weight <10th percentile that of
the overall obstetric population. Prenatal management
consisted of bed rest, high protein diet, and oral admin-
istration of allylestrenol 30 mg/day. The results were
positive with estimated fetal weight of 1,431 ± 284 gm at
33.8 ± 2.1 weeks’ gestation increased to 2,612 ± 451 gm
at 39.5 ± 1.8 weeks’ gestation. Average weekly increase
of body weight in these cases was significantly higher.
Maternal plasma estriol value increased from 2.1 ± 1.5 to
4.1 ± 3.6 mg/mL, urinary estriol increased from 14.0 ± 6.9
to 23.7 ± 11.2 mg/day, and serum progesterone increased
from 110 ± 14 to 133 ± 31 ng/mL 2 weeks after treatment.
All increases of the hormone values were statistically
significant. Therefore, the increases in maternal plasma
hormone levels were at least partly due to stimulation of
the placental function by allylestrenol.
Later, Kaneoka et al24 did a comparative study
between 75 cases given no medication vs 75 cases given
allylestrenol 30 mg/day until delivery. The difference
was statistically significant as the fetal weight aver-
aged 1,242 gm at the initial measurement at an average
32.7 weeks gestation when the diagnosis of IUGR was
made and 2,826 gm at the final measurement at 38.7 weeks
in the treatment group, while it averaged 1,281 gm at the
initial gestation and 2,498 gm at the final measurement
in the control group. Besides, the plasma estriol, urinary
estriol, and plasma hPL rose significantly in allylestrenol
group (Table 6).
Threatened Preterm Labor
Allylestrenol together with bed rest is an effective con-
sideration in the control of threatened preterm labor
with powerful pregnancy-maintaining and fetal weight-
promoting actions, and a remarkable lack of androgenic
activity. When used without tocolytics, recommended
dosage of allylestrenol for the treatment of threatened
preterm labor is 30 to 40 mg/day (two 5 mg tablets taken
3 to 4 times daily).25
In the study by Pandey et al,26 75 patients were
admitted between 28 and 36 weeks of gestation with
threatened preterm labor. Both primi- and multigravida
were included. The study group consisted of 50 patients
treated with 5 mg allylestrenol two tablets 8 hourly and
20 mg isoxsuprine 8 hourly, while the control group
consisted of 25 patients treated with 20 mg isoxsuprine
alone 8 hourly. In the study group, 82% continued
the pregnancy up to term compared with 65% in the
control group; besides, 70% babies weighed 2,500 gm
in the study group compared with 60% in the control
group. Therefore the combination of allylestrenol and
isoxsuprine was superior to isoxsuprine alone. The
study also showed that allylestrenol can be given with a
tocolytic drug, as no adverse effects have been reported.
The safety of allylestrenol both for the mother and the
baby, despite prolonged use, has been reestablished and
reconfirmed.
Pregnancy-induced Hypertension
Intrauterine growth retardation related to preeclamptic
toxemia (PET) improved particularly well as shown by
Kaneoka and Batra who compared their PET related
cases to others. Incidental case histories and other data
from numerous sources support the view that the PET
symptomatology of the mother is also antagonized. If
this is confirmed, it would fit well with what is known
about the relationship between impaired placental flow
and preeclampsia.24,27,28
ADVERSE EFFECTS
Safety studies suggest that allylestrenol usage at thera-
peutic dosage does not increase the rate of hypospadias
in the fetus.29,30 Allylestrenol is therefore beneficial over
other progestogens derived from 19-nortestosterone
which, besides their progestational activity, also show
some androgenic activity. Allylestrenol at therapeutic
dosage does not increase the incidence of hypospadia
in the fetus.
Table 5: Success rate in controlling recurrent abortion following
treatment with allylestrenol in some of the studies of various authors
Author
No. of patients
treated with
allylestrenol
Positive
results
Success
(%)
Borglin NE, 1960 6 4 67
Borglin NE and Eliasson C 25 19 76
Sas M et al 81 71 88
Sen Gupta 65 57 88
Grio R et al 89 61 69
Table 6: Success rate in controlling IUGR following treatment
with allylestrenol in some of the studies of various authors
Author
No. of patients
treated with
allylestrenol
Increase in mean
Infant birth
weight (gm)
Placental
weight (gm)
Kaneoka T
et al, 1982
22 212 (p < 0.01) Present
Kaneoka T
et al, 1983
30 223 (p < 0.01) Present
Singh J et al 136 Present Not mentioned
Kaneoka T
et al, 1986
75 616 (p < 0.001) Present
Narendra Malhotra et al
302
Allylestrenol has no serious side effects. It has no
known endocrinological side effects and thus, it is per-
fectly devoid of androgenic, estrogenic, and anabolic
properties.12,24,27,28,31-34
CONCLUSION
Allylestrenol has an interesting pharmacological profile,
combining potent pregnancy-maintaining and fetal
weight-promoting properties, with a notable absence of
androgenic activity. This probably explains the reason
for the extensive use of allylestrenol during pregnancy
in women with threatened abortion, selected cases of bad
obstetric history (habitual abortion), threatened preterm
labor, and IUGR for more than five decades. It exhibits a
unique trophoblastic cum placentotropic action (stimu-
lates the production of hormones and enzymes initially
from syncytiotrophoblast followed by placenta) not yet
been observed with any other progestogen, in addition
to having a highly selective β2-adrenergic action on the
uterus.
Studies have confirmed that allylestrenol did not
induce any anomalies or unwanted effects in both the
pregnant women and children. No risk of inducing
genital alterations, such as masculinizing effects of the
female fetus, was observed in human embryos deliber-
ately exposed to high-normal doses of allylestrenol given
to the mother before undergoing legal termination of
pregnancy. With strong pregnancy-maintaining and fetal
weight-promoting properties, and a notable absence of
androgenic activity, allylestrenol is an important consid-
eration in the management of the obstetric complications
as listed in our review.
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... Allylestrenol (AT) is an artificially synthesized progesterone, which can effectively treat abortion, TPTL, intrauterine growth restriction (6). Some studies have pointed out that AT has selective β-adrenergic effect mediated by nerves on myometrium β2 receptor, reducing myometrium activity, thus rapidly and effectively relaxing hypertonic myometrium within 24 h, and avoiding life-threatening emergencies of mothers, such as pulmonary edema and myocardial ischemia. ...
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Efficacy of allylestrenol combined with ritodrine on threatened premature labor (TPTL) and its influence on inflammatory factors in peripheral blood were investigated. A total of 206 cases of TPTL patients from 2014 to 2016 were collected in Zhongshan Hospital Affiliated to Fudan University, and 106 cases were treated with allylestrenol combined with ritodrine as a research group and 100 cases were treated with allylestrenol combined with magnesium sulfate as a control group. General information of patients was collected, and changes in the expression levels of IL-17, IL-10 and IL-6 were detected by enzyme-linked immunosorbent assay. Prolonged pregnancy time, success rate of fetal protection and average delivery time of patients were recorded. The adverse pregnancy conditions were compared, including the Apgar score of newborns, birth weight and adverse conditions, and postpartum hemorrhage volume and postpartum hospital stays in the two groups were recorded. Prolonged pregnancy time, success rate of fetal protection and average delivery time in the research group were significantly higher than those in the control group (P<0.05). After treatment, the levels of IL-17, IL-10 and IL-6 in serum of the two groups were significantly lower than those before treatment (P<0.05), and were significantly lower in the research group than in the control group (P<0.05). The average neonatal weight and Apgar score in the research group were significantly better than those in the control group (P<0.05). Postpartum hemorrhage, postpartum hospital stays and incidence rate of toxic side effects, neonatal death, malformation and asphyxia in the research group were significantly lower than those in the control group (P<0.05). Allylestrenol combined with ritodrine can significantly reduce the expression levels of IL-17, IL-10 and IL-6 in TPTL, reduce adverse pregnancy conditions, prolong gestational weeks, and has higher safety and better application value.
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