JOURNAL READING

Disusun oleh :
Dian Muflikhy Putri
NIM 112011101076

Dokter Pembimbing:
dr. Gogot Suharyanto Sp.OG

SMF ILMU OBSTETRI DAN GINEKOLOGI

RSD DR. SOEBANDI JEMBER
FAKULTAS KEDOKTERAN
UNIVERSITAS JEMBER
2015

JOURNAL READING

Disusun oleh :
Dian Muflikhy Putri
NIM 112011101076

Dokter Pembimbing:
dr. Gogot Suharyanto Sp.OG

Disusun untuk melaksanakan tugas Kepaniteraan Klinik Madya

SMF Ilmu Obstetri dan Ginekologi di RSD dr. Soebandi

SMF ILMU OBSTETRI DAN GINEKOLOGI

RSD DR. SOEBANDI JEMBER
FAKULTAS KEDOKTERAN
UNIVERSITAS JEMBER
2015

ii

Regmi et al., Gynecol Obstet 2012, 2:4

http://dx.doi.org/10.4172/2161-0932.1000125

Gynecology & Obstetrics

Research Article

Open Access

Progesterone for Prevention of Recurrent Preterm Labor after Arrested

Preterm Labor- A Randomized Controlled Trial
Mohan C. Regmi*, Pappu Rijal, Ajay Agrawal and Dhruba Uprety
Department of Obstetrics and Gynecology, BPKIHS, Dharan, Nepal

Abstract
Background: Preterm birth is the major cause of neonatal mortality and morbidity. In developing countries, its a
major health hazard. But there are very few evidence based interventions to prevent it. This study focus on prevention
of preterm birth.
Methods: A randomized controlled trial was undertaken in BP Koirala Institute of Health Sciences, where 60
patients were randomized into group 1 (n=29, weekly intramuscular Progesterone) and group 2 (n=31,no treatment)
after the arrest of preterm labor with tocolysis. Their latency period till delivery and recurrence of preterm labor and
neonatal outcomes were compared.
Results: There was significant reduction in recurrence of preterm labor and increase in latency period in
progesterone group. However neonatal outcomes were similar.
Conclusion: Progesterone is useful in reducing the recurrence of preterm labor in a patient who had preterm
labor.

Keywords: Progesterone; Preterm labor; Tocolysis

Introduction
Preterm birth is the major cause of neonatal mortality and
morbidity [1]. In addition, prematurity is strongly associated with
long-term developmental disabilities, accounting for 1 in 5 children
with mental retardation, 1 in 3 children with vision impairment, and
almost half of children with cerebral palsy. Importantly, low-birthweight infants who are spared significant neonatal morbidity are at
higher risk for cardiovascular disease (myocardial infarction, stroke,
and hypertension) and diabetes as adults [2]. The incidence of preterm
birth in developing countries is higher than in developed countries. So,
prevention of preterm birth is a public health priority. Pharmacological
therapy with a variety of drugs of different categories has been the
primary method of treating acute preterm labour [3]. Patients with
arrested preterm labor are at increased risk for recurrence, but to
this point, continued tocolytic treatment with any agent after arrest
of acute preterm labor is of questionable value in extending gestation
or improving outcome [3,4]. The efficacy of maintenance tocolytic
therapy after successful arrest of preterm labor remains controversial.
This question is not limited to the use of a specific drug as the data
are similar for terbutaline, magnesium sulphate, and calcium channel
blockers [3].

therefore, increases the -adrenergic tocolytic response [13]. Natural

progesterone is free of any disturbing teratogenic, metabolic, or
hemodynamic effects. This is not true for certain artificial progestagens
and -mimetics [14].
In 2003, two widely published double-blind trials, one of
daily vaginal progesterone suppositories and the other of weekly
intramuscular injections of 17alpha-hydroxyprogesterone, claimed
that the treatments effectively reduce the incidence of preterm birth in
women at risk of spontaneous preterm labour [15,16].
In study published in 2007, vaginal progesterone treatment
reduced the rate of preterm birth among women who were at high
risk for preterm birth because of a short cervix [17]. Progesterone has
long been considered important agents in the maintenance of uterine
quiescence and has been used extensively in primary and secondary
prevention of preterm labor [15,18].
We therefore, chose this pharmacological agent as the active drug
for our study. This randomized trial was designed to assess the use
of progesterone therapy in women who presented with symptoms
of preterm labor in preventing the recurrence of preterm labor and
increase the latency period after successful tocolysis.

Methods

Spontaneous preterm birth, that is preterm birth after labor

or rupture of the membranes, represents approximately 75% of all
preterm births [5]. Of all treatments evaluated for the prevention
of spontaneous preterm birth to date, progestational agents have
demonstrated the greatest promise. The exact mechanism of
progesterone in the prevention of preterm birth is not known,
although progesterone has been shown to prevent the formation of gap
junctions, to have an inhibitory effect on myometrial contractions, and
to prevent spontaneous abortion in women in early pregnancy after
excision of the corpus luteum [6-8]. Progesterone has also been shown
to delay parturition in animals [9]. In the last 40 years, progestins have
been administered to pregnant women for several reasons, including
threatening miscarriage, recurrent miscarriage, prevention of preterm
labor and luteal support during in vitro fertilization treatment [10-12].

Citation: Regmi MC, Rijal P, Agrawal A, Uprety D (2012) Progesterone for

Prevention of Recurrent Preterm Labor after Arrested Preterm Labor- A Randomized
Controlled Trial. Gynecol Obstet 2:125. doi:10.4172/2161-0932.1000125

Progesterone is useful in allowing pregnancy to reach its physiologic

term because at sufficient levels in the myometrium, it blocks the
oxytocin effect of prostaglandin F2 and -adrenergic stimulation and

Copyright: 2012 Regmi MC, et al. This is an open-access article distributed

under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the
original author and source are credited.

Gynecol Obstet
ISSN:2161-0932 Gynecology an open access journal

This randomized controlled trial was performed in the Department

of Obstetrics and Gynecology at B.P. Koirala Institute of Health
Sciences over the duration of 1.5 years from 2009 January to June 2010.
The Institutional Ethical Review Board approved this.

*Corresponding author: Mohan C. Regmi, Associate Professor, Department of

Obstetrics and Gynecology, BPKIHS, Dharan, Nepal, Tel: 9852049414; E-mail:
mohanchallo@yahoo.com
Received June 17, 2012; Accepted July 11, 2012; Published July 17, 2012

Volume 2 Issue 4 1000125

Citation: Regmi MC, Rijal P, Agrawal A, Uprety D (2012) Progesterone for Prevention of Recurrent Preterm Labor after Arrested Preterm Labor- A
Randomized Controlled Trial. Gynecol Obstet 2:125. doi:10.4172/2161-0932.1000125
Page 2 of 3

Women of 28-34 weeks period of gestation who were admitted

to the Obstetrics ward with preterm labor were involved in the study
after their labor was successfully arrested with tocolytics. Preterm
labor was defined as the simultaneous presence of contractions (> six
contractions in 30 min) and cervical changes, either shortening and/or
softening or dilation, by manual examination.
Recurrence of preterm labor was defined as recurrence of
contractions within 48 h after discontinuation of tocolysis and arrest of
contractions. Arrested preterm labor was defined as a 12-h contractionfree period after tocolytic therapy had been discontinued.
Inclusion criteria were singleton pregnancy, intact membranes,
no cerclage, cervical dilation of < 2 cm, and the dating of pregnancy
confirmed through first trimester ultrasound scanning or last
menstrual period. The cervical dilatation of 2 cm was taken according
to observation in the institute that > 2cm dilatation was associated with
poor response with tocolysis.
Exclusion criteria included clinical evidence of intra-amniotic
infection or pyelonephritis, medical complications contraindicating
tocolysis, evidence of fetal growth retardation, and sonographic
evidence of congenital anomalies inconsistent with life.
At admission, all patients had a haemogram, urine microscopy and
culture sensitivity and a high vaginal swab for culture and sensitivity.
All patients were given oral tocolytic, with an initial bolus of 30 mg
Nifedipine followed by 10 mg 8 hourly. All patients received antibiotic
prophylaxis consisting of Tablet Azithromycin 500 mg once a day for 5
days along with a five day course of oral Metronidazole. They were given
single course of Betamethasone, consisting of two 12 mg injections
during the first 24 h after admission. After arrested preterm labor was
diagnosed, the patient was counseled about the study and offered an
institutional review board-approved informed consent document.
Patients included in the study were randomized within 24 h of arrest
of labor. The random list was prepared with a computer generated
number list. Odds (progesterone, Group 1) and pairs (control, Group 2)
defined treatment allocation (Figure 1). Patients who were enrolled as
cases received Hydroxy progesterone Caproate 250 mg intramuscular
weekly till 37 completed weeks or earlier if they delivered. The
remaining patients were included as control subjects and received
no drugs. They were discharged for observation in the obstetric clinic
weekly. They were followed up either at clinic or by telephone if they do
not follow at clinic. The primary outcomes measure were the time until
delivery (latency period) and recurrence of preterm labor within 48 h
after discontinuation of tocolytic treatment and arrest of contraction.
Secondary outcome measures were incidence of low birth weight, and
perinatal morbidity (respiratory distress syndrome, intraventricular
hemorrhage, necrotizing enterocolitis, and proven sepsis) assessed at
the admission to Neonatal Intensive Care Unit (NICU).
Categorical data were tested for significance with the 2 and Fisher
exact tests. Continuous data were evaluated for normal distribution and
tested for significance with the Students t-test. Statistical significance
was defined as P < 0.05. All patients were included in the analysis.

There was significant increase in latency period in intervention arm

with decrease in incidence of recurrent preterm labor (Table 2).
There was no difference in neonatal outcome in both groups.
The birth weight, incidence of respiratory distress syndrome, need
of neonatal intensive care unit admission was similar in both groups
(Table 3).

Discussion
The study showed significant reduction in recurrent preterm labor
with the use of progesterone (38% vs. 64%). However neonatal outcomes
were comparable. In 2005, Roberta Mackenzie et al. [19] conducted a
meta-analysis evaluating the use of progesterone for women with high
risk of preterm birth. Three trials were eligible for inclusion. There
was a significant reduction in risk of delivery less than 37 weeks with
progestational agents. There was no significant effect on perinatal
mortality or serious neonatal morbidity. The finding was similar to our
study. In 2006, a meta-analysis by Aravinthan Coomarasamy et al. [20]
evaluated the use of progesterone in prevention of preterm delivery
in high risk patients. A total of nine randomized control trials were
evaluated comprising of about 500 patients. Meta-analyses showed
reductions in delivery rates before 37 weeks as well as in respiratory

Patients with arrested

preterm labor (n=60)

Group 1 (17-OHP)
n=29, followed till
delivery

Figure 1: A randomized controlled trial with tocolysis in two different groups.

Variables

17-OHP (n=29)

No therapy(n=31)

P value*

Age in years(mean)

23.24 3.47

22.81 3.73

0.642

Period of gestation at
admission(weeks)

32.62 1.72

32.90 1.94

0.552

Parity

1.48

1.29

Bishop Score

<3

<3

Nulliparity

*P value<0.05 was considered significant

Table 1: General character of both groups.
Variables

17-OHP (n=29)

No therapy (n=31)

P value*

Period of gestation at
delivery(weeks)

36.59 1.94

34.30 1.47

0.004

Recurrent preterm labor

11

20

0.039

Latency period (in days)

25.48 14.64

16.42 9.82

0.003

*P value<0.05 was considered significant

Table 2: Outcome of patients after intervention.

Results
There were total 60 patients at the study duration that fulfilled the
inclusion criteria and were randomized to receive either progesterone
or no treatment at all. Most of the patients admitted were from vicinity
of the institute in both groups. Only few of them were (n=8) were
illiterate. None of the patient had history of infertility. No patients had
history of previous preterm birth. None of the patients were nullipara
.There was no history of polyhydramnios. All the patients had Bishop
Score < 3.Both groups were comparable to each other (Table 1).
Gynecol Obstet
ISSN:2161-0932 Gynecology an open access journal

Group 2 (no Therapy )

n=31 followed till
delivery

Variables

17-OHP(n=29)

No therapy(n=31)

P value*

Birth weight(in kg)

2.903 0.596

2.781 0.444

0.372

Respiratory Distress Syndrome 3

0.938

Need of admission in NICU

Presence of sepsis

Low birth weight

0.856

*P value<0.05 was considered significant

Table 3: Neonatal outcomes.

Volume 2 Issue 4 1000125

Citation: Regmi MC, Rijal P, Agrawal A, Uprety D (2012) Progesterone for Prevention of Recurrent Preterm Labor after Arrested Preterm Labor- A
Randomized Controlled Trial. Gynecol Obstet 2:125. doi:10.4172/2161-0932.1000125
Page 3 of 3

distress syndrome with progestational agents. Most of the patients had

some of one or more risk factors for preterm birth prior to pregnancy.
Our study had homogenous comparable population prior to onset of
preterm labor. A similar study was carried out by Sedigheh BORNA
and Noshin SAHABI [21] in Tehran in 2004, where progesterone was
given to women after threatened preterm labor in one arm where as
another arm of patients received no treatment. There was significant
increase in mean latency until delivery, decrease in respiratory
distress syndrome, and decrease in low birth weight in progesterone
arm group. No significant differences were found between recurrent
preterm labor, admission to intensive care unit and neonatal sepsis
for the progesterone and control groups, respectively. Our study had
significantly decreased in incidence of recurrent preterm labor in
progesterone arm group.
All the study discussed above except that one by Sedigheh
BORNA and Noshin SAHABI, the comparison was difficult because
in other study it was to prevent the preterm labor with progesterone
with patients already having risk of preterm labor. Our study had
progesterone started after the arrest of preterm labor. The risk present
in our patient was episode of preterm labor arrested by tocolysis. There
was difference in type of progesterone use and the gestational age at
which they were recruited. In our study it was bit late (32 weeks).

9. Whitely JL, Hartmann PE, Willcox DL, Bryant-Greenwood GD, Greenwood

FC (1990) Initiation of parturition and lactation in the sow: effects of delaying
parturition with medroxyprogesterone acetate. J Endocrinol 124: 475-484.
10. Daya S, Gunby J (2004) Luteal phase support in assisted reproduction cycles.
Cochrane Database Syst Rev CD004830.
11. Oates-Whitehead RM, Haas DM, Carrier JA (2003) Progestogen for preventing
miscarriage. Cochrane Database Syst Rev CD003511.
12. Friedler S, Raziel A, Schachter M, Strassburger D, Bukovsky I, et al. (1999)
Luteal support with micronized progesterone following in-vitro fertilization using
a down-regulation protocol with gonadotrophin releasing hormone agonist: A
comparative study between vaginal and oral administration. Hum Reprod 14:
1944-1948.
13. Fuchs AR, Fuchs F (1984) Endocrinology of human parturition: a review. Br J
Obstet Gynaecol 91: 948-967.
14. Keelan JA, Myatt L, Mitchell MD (1997) Endocrinology and paracrinology of
parturition. In: Elder MG, Lamont RF, Romero R, (Eds) Preterm labor. Churchill
Livingstone, Philadelphia pp: 457-491.
15. da Fonseca EB, Bittar RE, Carvalho MH, Zugaib M (2003) Prophylactic
administration of progesterone by vaginal suppository to reduce the incidence
of spontaneous preterm birth in women at increased risk: A randomized
placebo-controlled double-blind study. Am J Obstet Gynecol 188: 419-424.
16. Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, et al. (2003)
Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone
caproate. N Engl J Med 348: 2379-2385.

The limitation of our study was small sample size and was not
compared with placebo. There was no blinding. So selection bias could
not be reduced.

17. Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH, et al. (2007)
Progesterone and the risk of preterm birth among women with a short cervix. N
Engl J Med 357: 462-469.

Conclusion

18. Noblot G, Audra P, Dargent D, Faguer B, Mellier G (1991) The use of micronized
progesterone in the treatment of menace of preterm delivery. Euro J Obstet
Gynecol Reprod Biol 40: 203-209.

Progesterone are promising agent to reduce the incidence of

recurrent preterm birth after arrest of preterm labor. Studies with
larger sample size with double blinding as well as earlier recruitment of
patient (at 28-32 weeks) would probably give more convincing results.
Acknowledgement
We would extend my sincere thanks to National Health Research Council for
supporting this research. We would like to extend sincere thanks to our institute
and all the participants of the study.

Conflict of Interest

19. Mackenzie R, Walker M, Armson A, Hannah ME (2006) Progesterone for the

prevention of preterm birth among women at increased risk: A systematic
review and meta-analysis of randomized controlled trials. Am J Obstet Gynecol
194: 1234-1242.
20. Coomarasamy A, Thangaratinam S, Gee H, Khan KS (2006) Progesterone for
the prevention of preterm birth: A critical evaluation of evidence. Eur J Obstet
Gynecol Reprod Biol 129: 111-118.
21. Borna S, Sahabi N (2008) Progesterone for maintenance tocolytic therapy after
threatened preterm labour: A randomised controlled trial. Aust N Z J Obstet
Gynaecol 48: 58-63.

The authors have no potential conflict of interest.

References
1. National Center for Health Statistics, NVSR (2001) Deaths and percentage of
total deaths for the 10 leading causes of neonatal and postneonatal deaths:
United States, 2001.
2. Gluckman PD, Hanson MA (2004) Living with the past: evolution, development
and patterns of disease. Science 305: 1733-1736.
3. Sanchez-Ramos L, Kaunitz AM, Gaudier FL, Delke I (1999) Efficacy of
maintenance therapy after acute tocolysis: a meta-analysis. Am J Obstet
Gynecol 181: 484-490.
4. Thornton JG (2005) Maintenance tocolysis. BJOG 112 : 118-121.
5. Meis PJ, Goldenberg RL, Mercer BM, Iams JD, Moawad AH, et al. (1998) The
preterm prediction study: risk factors for indicated preterm births. MaternalFetal Medicine Units Network of the National Institute of Child Health and
Human Development. Am J Obstet Gynecol 178: 562-567.
6. Garfield RE, Kannan MS, Daniel EE (1980) Gap junction formation in
myometrium: control by estrogens, progesterone, and prostaglandins. Am J
Physiol 238: C81-C89.
7. Allen WM, Reynolds SRM (1935) Physiology of the corpus luteum: the
comparative actions of crystalline progestin and crude progestin on uterine
motility in unanesthetized rabbits. Am J Obstet Gynecol 30: 309-318.
8. Csapo AI, Pulkkinen MO, Wiest WG (1973) Effects of luteectomy and
progesterone replacement therapy in early pregnant patients. Am J Obstet
Gynecol 115: 759-765.

Gynecol Obstet
ISSN:2161-0932 Gynecology an open access journal

Submit your next manuscript and get advantages of OMICS

Group submissions
Unique features:

User friendly/feasible website-translation of your paper to 50 worlds leading languages

Audio Version of published paper
Digital articles to share and explore

Special features:

200 Open Access Journals

15,000 editorial team
21 days rapid review process
Quality and quick editorial, review and publication processing
Indexing at PubMed (partial), Scopus, DOAJ, EBSCO, Index Copernicus and Google Scholar etc
Sharing Option: Social Networking Enabled
Authors, Reviewers and Editors rewarded with online Scientific Credits
Better discount for your subsequent articles

Submit your manuscript at: http://www.omicsonline.org/submission/

Volume 2 Issue 4 1000125

Abstrak
Latar belakang : kelahiran preterm merupakan penyebab utama mortalitas dan
morbiditas dari neonatal. Masalah ini menjadi sorotan di negara berkembang.
Tetapi, hanya ada sedikit tindakan medis yang efektif untuk mencegahnya.
Penelitian ini bertujuan pada pencegahan dari kelahiran preterm.
Metode : sebuah kontrol aacak dilakukan di institut ilmu kesehatan BP koirla,
dimana terdapat 60 pasien dimasukkan ke dalam 2 kelompok secara acak ( grup 1,
diberikan progesterone mingguan; grup 2, tidak diberikan perlakuan). Waktu
hingga persalinan terjadi dan kejadian rekurensi dari persalinan preterm dan
keadaan neonatal akan dibandingkan.
Hasil : terdapat hasill signifikan dalam pengurangan kejadian persalinan preterm
dan peningkatan periode latensi dari persalinan dalam kelompok yang diberi
progesteron, namun, kondisi neonatal hampir sama.
Kesimpulan. Progesteron memberikan hasil dalam mengurangi persalinan preterm
pada pasien yag telah mengalami persalinan preterm sebelumnya.
Pendahuluan
Persalinan preterm adalah penyebab utaama dari mortalitas dan
morbiditas

neonatal.

Prematuritas

berhubugan

erat

degan

disabilitas

perkembangan anak, seperti retardasi mental, gangguan penglihatan, dan cerebral

palsy. Lebih jauh lagi, bayi lahir dengan berat badan rendar lebih beresiko terkena
penyakit kardiovaskuler dan diabetes melitus pada masa dewasa. Insiden
kelahiran preterm pada negara berkembang lebih tinggi dari negara maju. Oleh
karena itu, pencegahan persalinan preterm menjadi masalah kesehatan yang
penting. Terapi farmakologis menjadi metode utama dalam mengobati persalinan
preterm. Pasien dengan persalinan preterm memiiliki tingkat rekurensi yang
tinggi.
Pasien

ynag

pernah

mengalami

persalinan

prematur

memiliki

kesempatan tinggi untuk kekambuhan. Khasiat pemeliharaan tokolitik masih

kontroversial. Begitu juga dengan penggunaan obat terbutalin , magnesium sulfat ,
dan calcium channelblockers

Kelahiran prematur spontan , yang lahir setelah pecahnya membran,

mewakili sekitar 75 % dari semuakelahiran prematur. Dari semua perawatan
dievaluasi untuk pencegahan kelahiran prematur spontan sampai saat ini , agen
progestasional memiliki potensi besar. Mekanisme yang tepat dari progesteron
dalam pencegahan kelahiran prematur tidak diketahui, meskipun progesteron telah
terbukti mencegah pembentukan gap persimpangan , memiliki efek penghambatan
pada kontraksi miometrium , dan untuk mencegah aborsi spontan pada wanita di
awal kehamilan setelah eksisi korpus luteum. Progesteron juga telah ditunjukkan
untuk menunda proses kelahiran pada hewan. Dalam 40 tahun terakhir , progestin
telah diberikan kepada wanita hamil karena beberapa alasan, abortus iminens,
abortus inibitus, pencegahan persalinan preterm.
Progesteron berguna dalam memungkinkan kehamilan mencapai aterm
pada kadar yang cukup dalam miometrium, bekerja denagn memblok efek
oksitosin prostaglandin F2 dan stimulasi - adrenergik dan oleh karena itu,
meningkatkan respon tokolitik - adrenergik. Alam progesteron bebas dari
mengganggu teratogenik , metabolisme , atau efek hemodinamik . Hal ini tidak
berlaku untuk progestagens buatan tertentu dan mimetics.
Pada tahun 2003 , dua dipublikasikan secara luas percobaan doubleblind, salah satu harian supositoria progesteron vaginal dan lain mingguan
suntikan intramuskular 17alpha - hidroksiprogesteron , mengaku bahwa
perawatan efektif mengurangi kejadian kelahiran prematur di wanita yang berisiko
persalinan prematur spontan.
Dalam studi yang dipublikasikan pada tahun 2007 , pengobatan
progesteron vaginal mengurangi tingkat kelahiran prematur pada wanita yang
berada di tinggi risiko kelahiran prematur karena leher rahim pendek. Progesteron
memiliki lama dianggap agen penting dalam pemeliharaan uterus ketenangan dan
telah digunakan secara luas di primer dan sekunder pencegahan persalinan
prematur.

Oleh karena itu kita , memilih agen farmakologis ini sebagai obat aktif
untuk penelitian kami . Uji coba secara acak ini dirancang untuk menilai
penggunaanterapi progesteron pada wanita yang disajikan dengan gejalapersalinan
prematur dalam mencegah kekambuhan persalinan prematur dan meningkatkan
masa laten setelah sukses tokolisis.
Metode
Uji coba terkontrol secara acak ini dilakukan di Departemen Obstetri
dan Ginekologi di B.P. Koirala Institut Kesehatan Ilmu selama durasi 1,5 tahun
dari Januari 2009 hingga Juni 2010 . The Institutional Ethical Review Board
disetujui ini .
Wanita periode 28-34 minggu kehamilan yang dirawat ke bangsal
Obstetri dengan persalinan prematur yang terlibat dalam penelitian ini setelah
kerja mereka berhasil ditangkap dengan tokolitik . prematurtenaga kerja
didefinisikan sebagai keberadaan simultan kontraksi ( > enam kontraksi dalam 30
menit ) dan perubahan serviks , baik shortening dan / atau pelunakan atau
pelebaran , dengan pemeriksaan manual.
Kekambuhan persalinan prematur didefinisikan sebagai kambuhnya
kontraksi dalam waktu 48 jam setelah penghentian tokolisis dan penangkapan
kontraksi. Persalinan prematur ditangkap didefinisikan sebagai 12 - h
contractionfree periode setelah terapi tokolitik telah dihentikan.
Kriteria inklusi adalah kehamilan tunggal , membran utuh, ada cerclage ,
dilatasi serviks dari < 2 cm , dan kencan kehamilan dikonfirmasi melalui trimester
pertama ultrasound scanning atau terakhir periode menstruasi. Dilatasi serviks
dari 2 cm diambil sesuai pengamatan di lembaga yang > 2 cm dilatasi dikaitkan
dengan
Tanggapan miskin dengan tokolisis .
Kriteria eksklusi meliputi bukti klinis intra amnion infeksi atau
pielonefritis, komplikasi medis kontraindikasi tokolisis , bukti retardasi
pertumbuhan janin , dan sonografi bukti anomali kongenital tidak konsisten
dengan kehidupan .

Saat masuk, semua pasien memiliki haemogram, mikroskop urin dan

sensitivitas budaya dan swab vagina tinggi untuk kultur dan sensitivitas. Semua
pasien diberi tokolitik lisan, dengan bolus awal 30 mg Nifedipine diikuti oleh 10
mg 8 jam. Semua pasien menerima antibiotikprofilaksis terdiri dari Tablet
Azitromisin 500 mg sekali sehari selama 5 hari bersama dengan kursus lima hari
oral Metronidazole. Mereka diberi Tentu saja satu Betametason, yang terdiri dari
dua 12 mg suntikan selama 24 jam pertama setelah masuk. Setelah persalinan
prematur ditangkap adalah didiagnosis, pasien konseling tentang penelitian dan
menawarkan Ulasan kelembagaan dewan disetujui dokumen informed consent.
Pasien dimasukkan dalam penelitian ini diacak dalam waktu 24 jam dari
penangkapan tenaga kerja. Daftar acak disiapkan dengan komputer yang
dihasilkan
daftar nomor. Odds (progesteron, Kelompok 1) dan pasang (kontrol, Kelompok 2)
alokasi pengobatan didefinisikan (Gambar 1). Pasien yang terdaftar sebagai kasus
yang diterima Hydroxy progesteron kaproat 250 mg intramuskular mingguan
sampai 37 minggu selesai atau sebelumnya jika mereka disampaikan. Itu pasien
yang tersisa dimasukkan sebagai subyek kontrol dan menerima tidak ada obat.
Mereka dipulangkan untuk observasi di klinik kebidanan mingguan. Mereka
ditindaklanjuti baik di klinik atau melalui telepon jika mereka lakukan tidak
mengikuti di klinik. Ukuran hasil utama adalah waktu sampai pengiriman (masa
laten) dan kekambuhan persalinan prematur dalam waktu 48 jam setelah
penghentian pengobatan tokolitik dan penangkapan kontraksi. Ukuran hasil
sekunder adalah kejadian berat badan lahir rendah, dan morbiditas perinatal
(sindrom

gangguan

pernapasan,

intraventrikular

perdarahan,

necrotizing

enterocolitis, dan terbukti sepsis) dinilai pada yang masuk ke Neonatal Intensive
Care Unit (NICU).
Data kategorikal diuji signifikansi dengan 2 dan Fisher tes yang tepat .
Data kontinyu dievaluasi untuk distribusi normal dan diuji signifikansi dengan t test pelajar . signifikansi statistik didefinisikan sebagai P < 0,05 . Semua pasien
dimasukkan dalam analisis .

Ada Total 60 pasien pada durasi studi yang memenuhi kriteria inklusi
dan diacak untuk menerima baik progesteron atau tanpa pengobatan sama sekali .
Sebagian besar pasien mengaku berasal dari sekitarnya dari lembaga pada kedua
kelompok . Hanya sedikit dari mereka yang ( n = 8 ) yang buta huruf . Tak satu
pun dari pasien memiliki riwayat infertilitas . Tidak ada pasiensejarah kelahiran
prematur sebelumnya . Tidak ada pasien yang nulipara. Ada Ada riwayat
polihidramnion . Semua pasien memiliki Bishop Skor < kelompok 3. Baik
sebanding dengan satu sama lain ( Tabel 1).

Gambar 1. Kelompok kontrol acak dengan tokolisis

Variabel

17-OHP (n=29)

Tanpaterapi(n=31)

Nilai P

Usia (rata-rata)

23.24 3.47

22.813.73

0.642

Usia fgestasi

32.621.72

32.901.94

0.552

Paritas

1.48

1.29

bishop score

<3

<3

Nulliparitas

Gambar 1. Karakter umum dari kedua grup

Hasil
Ada peningkatan yang signifikan dalam periode laten di lengan
intervensi dengan penurunan kejadian persalinan prematur berulang ( Tabel 2 ) .

Tidak ada perbedaan dalam hasil neonatal pada kedua kelompok. Berat
lahir, kejadian sindrom gangguan pernapasan , perlu neonatal unit perawatan
intensif tiket masuk adalah serupa pada kedua kelompok ( Tabel 3 ) .
Diskusi
Hasil penelitian menunjukkan penurunan yang signifikan dalam
persalinan prematur berulang dengan penggunaan progesteron ( 38 % vs 64 % ) .
Namun hasil neonatal sebanding . Pada tahun 2005 , Roberta Mackenzie et al .
melakukan meta - analisis mengevaluasi penggunaan progesteron untuk wanita
dengan tinggi risiko kelahiran prematur . Tiga uji coba yang memenuhi syarat
untuk dimasukkan . di sana adalah penurunan yang signifikan dalam risiko
kelahiran kurang dari 37 minggu dengan agen progestasional . Tidak ada efek
yang signifikan pada perinatal mortalitas atau morbiditas neonatal serius . Temuan
ini mirip dengan kami studi . Pada tahun 2006 , sebuah meta - analisis oleh
Aravinthan Coomarasamy et al.mengevaluasi penggunaan progesteron dalam
pencegahan kelahiran prematur pada pasien berisiko tinggi . Sebanyak sembilan
percobaan terkontrol secara acak yang dievaluasi terdiri dari sekitar 500 pasien .
Meta - analisis menunjukkan penurunan tarif pengiriman sebelum 37 minggu serta
pernapasansindrom gangguan dengan agen progestasional . Sebagian besar pasien
memiliki beberapa dari satu atau lebih faktor risiko kelahiran prematur sebelum
kehamilan .
Penelitian kami memiliki populasi sebanding homogen sebelum onset persalinan
prematur . Sebuah studi serupa dilakukan oleh Sedigheh BORNA dan Noshin
Sahabi [ 21 ] di Teheran pada tahun 2004 , di mana progesteron adalah diberikan
kepada wanita setelah persalinan prematur mengancam di satu tangan dimana
lengan lain dari pasien tidak menerima pengobatan . Ada signifikanpeningkatan
rata-rata latency sampai melahirkan , penurunan pernapasan distress syndrome ,
dan penurunan berat badan lahir rendah di progesteron kelompok lengan . Tidak
ada perbedaan signifikan yang ditemukan antara berulang persalinan prematur ,
masuk ke unit perawatan intensif dan sepsis neonatal untuk progesteron dan
kelompok kontrol , masing-masing. Penelitian kami memiliki secara signifikan

menurun pada kejadian persalinan prematur berulang di progesteron lengan

kelompok .
Semua penelitian yang dibahas di atas kecuali bahwa satu per Sedigheh
BORNA dan Noshin sahabi , perbandingan itu sulit karena dalam penelitian lain
adalah untuk mencegah persalinan prematur dengan progesteron dengan pasien
yang sudah memiliki risiko persalinan prematur . Penelitian kami memiliki
progesteron mulai setelah penangkapan persalinan prematur . Saat ini risiko pada
pasien kami adalah episode persalinan prematur ditangkap oleh tokolisis . di sana
perbedaan dalam jenis penggunaan progesteron dan usia kehamilan di yang
mereka direkrut . Dalam penelitian kami itu agak terlambat ( 32 minggu ).
Keterbatasan dari studi kami adalah ukuran sampel yang kecil dan tidak
dibandingkan dengan plasebo . Tidak ada menyilaukan . Jadi bias seleksi bisa
tidak dikurangi .