Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04960982 |
| Other study ID # |
'RMPCOS2021 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
March 1, 2018 |
| Est. completion date |
May 1, 2021 |
Study information
| Verified date |
July 2021 |
| Source |
Kafrelsheikh University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
Introduction: Elevated levels of androgen and insulin-resistant have been implicated in
recurrent miscarriage in women with PCOS. Published data are scarce on androgen level and
cervical length of women with and without PCOS and a history of miscarriage.
Aim: The aim of this study was to investigate the levels of testosterone (TT), Sex Hormone
Binding Globulin (SHBG), Dehyroepiandrostenedione (DHEA) and cervical length in Egyptian
women with and without history PCOS and history of RM during pregnancy .
Method: Pregnant women with (n=38) and without (n=40) PCOS and history of recurrent
miscarriages were recruited from the Obstetrics Department, Alagoza Hospital, Cairo, Egypt.
Healthy pregnant women without PCOS and history of RM (n=40, HC) were also recruited. TT,
SHBG,DHEA and Sex Hormone Binding Globulin (SHBG) level and cervical length were assessed at
first, second and the third trimester or at the start of miscarriage
Description:
Introduction
Recurrent miscarriage (RM )is defined as the loss of three of more consecutive pregnancies
before 20 weeks gestation (Royal College of Obstetricians & Gynaecologists 2011, Practice
Committee of American Society for Reproductive Medicine 2013). The prevalence of RM varies
from country to country and within communities within the country. It tends to be higher in
developing countries. However it effects 1% to 2%of women (Jeve et al., 2014, Green-top
Guideline No. 17).Other studies have reported incidences of RM between 0.5% and 2.3 %
(Christiansen et al.,2007, Stirrat et al., 1990, Alberman et al., 1988).
Currently the established risk factors of RM include hormonal associated conditions
(Stephenson et al.,1996, Fox-Lee et al., 2007) , uterine abnormalities (including adhesions
post-surgery) (Rimbizis et al.,2001, Salim et al.,2003) anti-phospholipid syndrome Thrombotic
(Greer et al., 2003) , chromosomal and genetic (Braekeleer et al., 1990 , Clifford et
al.,1994, Stephenson et al., 2006, Franssen et al., 2006) conditions .Indeed some researchers
consider PCOS as a risk factor, However some don't.
Approximately 8% to 12% of RM is due to endocrine causes mainly due to hyperandrogenism and
hyperinsulinemia in PCOS (Smith et al., 2011, Witchel et al., 2019, Rai et al., 2000) .
Little research focuses directly on the effect of PCOS during gestation and how that can be
linked to poor pregnancy outcomes. However, there is a positive correlation between increased
risk of miscarriage and hyperhomocysteinemia in insulin resistant patients, a common
component of PCOS (Chakraborty et al.,2013).
The current literature providing conflicting views on androgen levels effecting pregnancy in
PCOS patients some clarity is required as to whether its elevation impacts pregnancy. Not
only that, but the is limited published data which compared the androgen and cervical length
at different gestational periods of women with history of miscarriage either due to PCOS or
for unknown reasons.
Cervical cerclage (CC) is one of the management options offered to patient who has history of
midterm miscarriage. The efficacy of CC in management is still doubtable.
Aim The aim of this study was to investigate the levels of testosterone (TT), Sex Hormone
Binding Globulin (SHBG), Dehyroepiandrostenedione (DHEA) and cervical length in women with
and without history PCOS and history of RM during pregnancy .
Subjects and Methods
- Subjects
Participants of the study are women with (n=38) and without PCOS (n=40) and history of RM
were recruited during their first antenatal visit from Al-Agoza Hospital, Cairo, Egypt. They
were recruited during their first antenatal visit. Similarly pregnant women without PCOS
(n=40) with no history of RM were recruited. Detailed demographic, medical and obstetric
history was documented.
The inclusion criteria for the study were women aged 23 to 40 years at the time of enrolment
into the study. The exclusion criteria for all participants included any other diagnosed
medical condition link with increased risk of miscarriage, including thyroid status and
gestational diabetes. All participants examined at the time of recruitment.
The control group were matched for age and BMI with no previous history of RM.
This study was conducted in line with the human experimentation guidelines, dictated by the
Helsinki declaration. The procedures used were approved by local ethical committee and
conducted in line with the practices of Al-Agoza Hospital, Cairo, Egypt. All patients within
the study were briefed on the procedures and protocol that would take place and written
consent was obtained before induction into the study.
- Methods
Confirmation of the pregnancy was made by beta-human chorionic gonadotrophin (Bhcg ) plus
ultrasound scan and clinical history in case of miscarriage.
Diagnosis for patients with recurrent miscarriage was in concordance with the guidelines
defined by the Royal College of Obstetricians and Gynaecologists; the loss of three or more
consecutive pregnancies (Royal College of Obstetricians & Gynaecologists 2011 ).The diagnosis
of PCOS was based on Rotterdam 2003 Criteria (Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus
Workshop Group 2004 ) which require two of the following; Oligo- or anovulation, Clinical
and/or biochemical signs of hyperandrogenism or Polycystic ovaries and exclusion of other
related disorders.
Blood Samples were collected by a professional trained in phlebotomy at the time points ;
first, second and the third trimester or at the start of miscarriage .Samples were analysed
for TT, SHBG,SHBG and DHEA using The ADVIA Centaur® XPT Immunoassay System - Siemens
(https://www.siemens-healthineers.com/en-uk/immunoassay/systems/advia-centaur-xpt#TECHNICAL_S
PECIFICATIONS).This system is easy to use where samples and reagents which could be loaded or
without pausing the system. Also it doesn't require daily set up procedure and implement new
assays immediately with one easy scan of a test definition bar code.
It requires 10-200 μL per test. it offers Automatic dilution varies by assay, up to 1:2500.
The reagent capacity on board is 30 assays.
Similarly, cervical length was also measured at first, second and the third trimester or at
the start of miscarriage .It was measured via transvaginal ultrasound (Berghella et
al.,1997). The Voluson™ E8 ultrasound system is used for this study
(https://www.gehealthcare.com/products/ultrasound/voluson/voluson-e8 ). The data was recorded
by measuring the distance between the external os of the cervix and to where the cervix is
closed defined by the apex of the funnelling of the membranes (Berghella et al., 1997) .
All patients within the RM groups attended cerclage treatment during the second trimester,
this included elective and emergency elective procedures. Patients presented at the time of
delivery or for recording of miscarriage where gestational age, gender of the fetus/baby and
whether it was a live birth was noted.
