Showing posts with label miscarriage. Show all posts
Showing posts with label miscarriage. Show all posts

Tuesday, June 12, 2018

Use of antimycotics in early pregnancy is not linked to spontaneous abortion


Exposure to antifungals Clotrimazole and miconazole during pregnancy for Vulvovaginal candidiasis (VVC) is not associated with increased risk of spontaneous abortion says the results of a cohort study published in June issue of American Journal of Obstetrics and Gynecology.

VVC is more frequent in pregnancy possibly because of higher estrogen levels and higher glycogen content in vaginal secretions; thereby, creating a favorable environment for the yeast to thrive and grow. It is estimated that about 10% of pregnant women in the USA will have a yeast infection at any given time.


Topical clotrimazole and miconazole are the treatment of choice for VVC in pregnancy. They are easily available over the counter and are known to be safe in pregnancy. A recent study has suggested an increased risk of miscarriage by using these azoles.

The researchers from Beer-Sheva, Israel conducted this historical study to investigate the risk of spontaneous abortion after treatment with vaginal antimycotics.

Data was gathered on all clinically apparent pregnancies over a period of 6 years (2003-2009) at the Soroka Medical Center, Clalit Health Services, Beer-Sheva, Israel. Databases with information on medicines dispensed to these patients and information on births and spontaneous abortions were linked together.

Statistical analysis was done by time-varying Cox regression models adjusted for maternal demographics like age, ethnicity, tobacco use, and the year of admission; the presence of chronic diseases like diabetes mellitus, hypothyroidism, obesity, hypercoagulable or inflammatory conditions; and reproductive and contraceptive history.

A total of 65,457 pregnancies were included in the analysis of which 58,949 (90.1%) ended with birth and 6508 (9.9%) with a spontaneous abortion.

Out of which 3246 (5%) pregnancies received vaginal antifungal drugs until the 20th week of gestation: (2712 (4.2%) were exposed to clotrimazole and 633 (1%) to miconazole.

Exposure to vaginal antifungals as a group was not linked to spontaneous abortion (adjusted hazard ratio, 1.11; 95% confidence interval, 0.96–1.29). Individually clotrimazole and miconazole were also not associated with spontaneous abortion.  

There was no dose-response relationship observed between the antifungals and spontaneous miscarriages.

The authors concluded that vaginal use of antimycotics is not linked to spontaneous abortion.






Monday, April 23, 2018

Addition of 24-chromosome microarray analysis to standard testing identifies a probable or definitive cause in over 90% of recurrent miscarriages

http://www.ucl.ac.uk/

The new method of 24 Chromosome Microarray, or comprehensive chromosomal screening when added to the standard Recurrent Pregnancy Loss (RPL) evaluation of American Society for Reproductive Medicine (ASRM) could provide a probable or definitive cause in over 90% of patients reports the result of a small prospective cohort study published 1 April 2018 in Journal of Human Reproduction.

In the absence of definitive etiologies and treatment strategies, RPL is one of the most frustrating and difficult to treat entity in reproductive medicine. It affects 2%-5% of couples and a cause can be found only in 50% of the couples after undergoing the standard ASRM workup.

This single-center study included 100 patients from a private RPL clinic from 2014 to 2017. The maternal age was between 26 to 45 years.

All 100 women had two or more pregnancy losses, with a complete evaluation for RPL as defined by the ASRM, and miscarriage tissue evaluated by 24-chromosome microarray analysis after their second or subsequent miscarriage.

In 95 of 100 patients, a probable or definitive cause of pregnancy loss was identified when 24-chromosome microarray analysis was combined with the standard ASRM RPL workup evaluation at the time of second or subsequent miscarriage.

The standard ASRM RPL workup done alone could only identify an abnormality or cause of miscarriage in 45 of 100 patients while 24-chromosome microarray analysis identified an abnormality in 67 of 100 patients when performed as the initial test on miscarriage tissue.

In only 5 of 100 patients, no cause could be found even after combined testing by ASRM RPL workup and 24-chromosome microarray analysis.

The authors concluded that combining the standard workup and genetic evaluation on miscarriage tissue obtained at the time of the second and subsequent pregnancy losses could offer much more answers towards the probable or definitive cause of RPL. It should be routinely offered to couples who have had two or more consecutive pregnancy losses.


Tuesday, September 12, 2017

Low serum AMH levels doubles the risk of miscarriage after in vitro fertilization–embryo transfer

geneticliteracyproject.org
Patients with low serum antimüllerian hormone (AMH) levels face a  33% higher risk of miscarriage as compared to women with high AMH says results of a university affiliated single center cohort study published in September issue of Journal Fertility and Sterility.

The researchers looked at AMH levels of more than 2,000 patients undergoing 2,688 IVF cycles with fresh oocytes, who attained a clinical pregnancy after IVF-ET. These patients had their centralized serum AMH levels measured within 1 year before they underwent embryo transfer.

It was seen that patients with reduced AMH levels suffered significantly more pregnancy losses as compared to women with normal AMH levels which remained the same after controlling for age and ovarian response to stimulation, which indicates that AMH is also a marker of reproductive potential and not just the number of oocytes.

AMH levels lower than 1.61 ng per mL were considered low but a definite cut-off could as the values vary by the test type.

A subgroup analysis of women according to age showed that in women older than 33 (34-36 and 37 and above) low serum AMH was associated with 33% miscarriage rate as compared to women with AMH > than 5.6 ng per mL, which was nearly twice as compared to women less than 33 years.

On the other hand, in women aged 33 and below, low serum AMH resulted in 22% rate of miscarriage, compared with about 13% among women with higher AMH levels, which was not statistically significant. But, when age was taken as single variable, the results were statistically significant.

The paper was also presented at October 2016 Annual meeting of the American Society for Reproductive Medicine in Salt Lake City, Utah.

No genetic testing of the embryos transferred or expelled products of conception was carried out to link the miscarriages to abnormalities such as aneuploidy.





Monday, October 17, 2016

News from American Society for Reproductive Medicine (ASRM) 2016 Scientific Congress-- Low AMH levels predict poor outcome in patients undergoing IVF-ET.

Clinical Pearls:

  • Patients aged >34 years with low AMH levels displayed poorer IVF-ET outcome particularly, higher miscarriage rates that is not dependent on age and ovarian response to COH.



American Society for Reproductive Medicine (ASRM) 2016 Scientific Congress is currently ongoing (October 15 – 19) at  Salt Lake City, Utah. Some selected abstract and news from the conference.

Anti-Müllerian Hormone (AMH) has long been known to provide insight into ovarian function. It is produced by small, growing follicles, thus providing us with quantitative information on ovarian reserve.

While AMH levels predict the treatment outcome in controlled ovarian hyperstimulation, no data is available on its role in predicting miscarriages in patients undergoing IVF-ET. [1] Researchers are more and more interested to evaluate its role in oocyte competence and embryo health.

Results of a prospective study by  Tarasconi B et al at the ASRM 2016 conference shows the role played by levels of AMH and subsequent miscarriage rate in patients undergoing IVF-ET. [2] The paper is also published in a special supplement of Journal Fertility and Sterility.

The study authors examined 2,365 infertile women undergoing 2,688 IVF-ET cycles. All the women included in the study had serum AMH tested as reference with ELISA. Women were classified into 3 age groups: ≤33 years (n=1,033), 34-36 years (n=690) and ≥37 years (n=965) and into 3 different AMH groups: Low AMH (0.04-1.60 ng/mL; n=540), Intermediate AMH (1.61-5.59 ng/mL; n=1,608), and High AMH (5.60-35.00 ng/mL; n=540).

After analyzing the data by binary logistic regression, it was seen that clinical pregnancy and live birth rate were directly proportional to levels of AMH, with miscarriage rate being highest in the low AMH level group.

The results were statistically significant in older women in the two age groups of 34-36 years and ≥37 years.

When the whole population was included as one variable, regression analysis showed direct association between patient’s AMH levels and rate of miscarriages independent of age and number of oocyte retrieved.

The study findings support the hypothesis that AMH levels are biomarker of oocyte and embryo reproductive health beside predicting number of oocyte obtained by COH. 


[2] http://www.fertstert.org/article/S0015-0282(16)61512-1/fulltext

Tuesday, October 4, 2016

Adverse pregnancy and neonatal outcome in subclinical hypothyroidism: A Systematic Review and Meta-Analysis

Clinical Pearls:
  • Subclinical hypothyroidism (SCH) is defined as elevated TSH levels with normal serum levels of thyroxine (T4). Recently ATA redefined the upper limit of TSH during pregnancy to 2.5 mIU/L during the first trimester and 3.0 mIU/L during the second and third trimesters
  • The review confirms the association of SCH during pregnancy with multiple adverse maternal and neonatal outcomes, but there is not sufficient evidence to support the use of levothyroxine therapy to mitigate this association.
  • Decision to start levothyroxine in such patients should be taken after an open and well informed discussion between patients and physicians.

  
Routine screening of all pregnant women for hypothyroidism is debatable because of conflicting data from previous studies. ACOG and American Thyroid Association (ATA) recommends against universal first trimester screening of pregnant women.

Subclinical hypothyroidism (SCH) is defined as elevated TSH levels with normal serum levels of thyroxine (T4). Recently ATA redefined the upper limit of TSH during pregnancy to 2.5 mIU/L during the first trimester and 3.0 mIU/L during the second and third trimesters.[1]

When screened according to the updated criteria’s, nearly 15% pregnant women in United states have SCH, which is almost 5 times the previous prevalence.

Many studies have reported adverse maternal and neonatal outcomes in pregnancy with SCH that includes an array of problems like including recurrent pregnancy loss, preterm delivery, gestational diabetes, gestational hypertension, preeclampsia, placental abruption, premature rupture of membranes, intrauterine growth restriction, low birth weight, small for gestational age, low Apgar score, and neonatal death.

Some studies also report increased risk of cognitive deficits with rising TSH levels.

Other studies have not found any statistically significant association between SCH and adverse pregnancy outcomes.

This systemic review and meta-analysis estimates the effect of SCH on pregnancy outcome with patients who are euthyroid and the effect of levothyroxine on preventing the adverse pregnancy outcomes.

The study was published in the April issue of Journal Thyroid.[2]

The main outcome measures were pregnancy loss (miscarriage, IUD and fetal loss). Other outcome measure included various other complications of pregnancy.

Comprehensive search of data base from inception to January 2015, identified 1108 potentially eligible studies, of which 18 cohort studies comprising of total 3995 pregnant women with SCH were eligible. 

After meta-analysis and sensitivity analysis, it was seen that women with SCH were at higher risk for pregnancy loss, placental abruption, PROM, and neonatal death compared with euthyroid pregnant women.

The study also showed the prevalence of inconsistencies in defining SCH in different studies, absence of trimester specific range and cutoff that is used to start treatment with levothyroxine.

The ATA guidelines recommend treatment of pregnant women with SCH and positive TPO antibodies (Level B, fair evidence—USPSTF), but found insufficient evidence to recommend for or against universal levothyroxine treatment in pregnant women with SCH and negative TPO antibodies (Level I—USPSTF).[3]

The Endocrine Society panel recommends levothyroxine replacement in all pregnant women with SCH (weak recommendation, low-quality evidence).[4]although this will result in treating nearly 15% of pregnant women with levothyroxine, the guidelines panel opine that it will gain the benefits of replacing levothyroxine and reducing adverse effects as iatrogenic hyperthyroidism is unknown. 

The review stresses the importance and need of a large randomized trial to study the effects of levothyroxine supplementation on patients with SCH.  

To conclude, the review confirms the association of SCH during pregnancy with multiple adverse maternal and neonatal outcomes, but there is not sufficient evidence   to support the use of levothyroxine therapy to mitigate this association.

Clinicians and patients must have a frank and informed discussion with the patients on use of levothyroxine in patients with SCH, while we wait for larger trials to be conducted on patients with SCH and use and benefits of levothyroxine.




[1]A Stagnaro-Green, M Abalovich, E Alexander, F Azizi, J Mestman, R Negro, A Nixon, EN Pearce, OP Soldin, S Sullivan, W Wiersinga 2011 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 21:1081–1125.
[2] Maraka Spyridoula, Ospina Naykky M. Singh, O'Keeffe Derek T., Espinosa De Ycaza Ana E., Gionfriddo Michael R., Erwin Patricia J., Coddington Charles C. III, Stan Marius N., Murad M. Hassan, and Montori Victor M.. Thyroid. April 2016, 26(4): 580-590. doi:10.1089/thy.2015.0418.
[3] A Stagnaro-Green, M Abalovich, E Alexander, F Azizi, J Mestman, R Negro, A Nixon, EN Pearce, OP Soldin, S Sullivan, W Wiersinga 2011 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 21:1081–1125.
[4] L De Groot, M Abalovich, EK Alexander, N Amino, L Barbour, RH Cobin, CJ Eastman, JH Lazarus, D Luton, SJ Mandel, J Mestman, J Rovet, S Sullivan 2012 Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 97:2543–2565.

Wednesday, September 28, 2016

Morning Sickness in early pregnancy linked to lower risk of miscarriages and still births.

Nausea and vomiting in early pregnancy affects 50-80% of pregnant women. Researchers have linked its etiology to imbalance in carbohydrate metabolism, rising hormonal levels in pregnancy, psychosomatic factors  evolutionary survival adaptation which protects pregnant mothers and their babies from food poisoning

 Few  observational studies in the past have documented that incidence of pregnancy loss is lower in patients who have morning sickness in first trimester.

A new study published in the in the journal JAMA Internal Medicine[1] found that women who suffer from nausea and vomiting in the first trimester have 50% less chance of miscarriage.

The study is a result of secondary data analysis of a Randomized Control Trial (RCT) examining Effects of Aspirin in Gestation and Reproduction (EAGeR) Trial.[2] The EAGeR study is a multi-site, double-blinded randomized trial designed to assess the effects of low-dose aspirin on implantation and pregnancy outcome carried out by researchers at NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and other institutions.

The secondary analysis was limited to women who had a pregnancy confirmed by positive human chorionic gonadotropin (hCG) test, had a history of at least one pregnancy loss. A total of 797 study subjects was recruited. The women kept a daily diary for nausea and vomiting from week 2 to week 8 of pregnancy, and monthly thereafter.

Out of 797 pregnancies, 188 ended in loss (23.6%), and at the end of 8 weeks about 57.3 percent of the women reported experiencing nausea and 26.6 percent reported nausea with vomiting. 
In this cohort of women, it was seen that nausea alone or nausea with vomiting during pregnancy were associated with nearly 50%-75% reduction in the risk for pregnancy loss. When the analysis was done for peri-implantation pregnancy loss, the results were similar but they were not statistically significant.

Younger women (age <25 years) suffered much more with nausea and vomiting as compared to older women.

The association persisted even after accounting for confounding factors like maternal stress, alcohol intake, caffeine intake, smoking, fetal sex, multiple-fetal gestation, and karyotype.

Stefanie Hinkle, the lead author and a researcher at the national institute said "Our study evaluates symptoms from the earliest weeks of pregnancy, immediately after conception, and confirms that there is a protective association between nausea and vomiting and a lower risk of pregnancy loss.” But, was not sure whether the study results could be applied to primigravida.

She also went to stress that women with no nausea or vomiting should not be alarmed as a result of this study. "Every pregnancy is different and just because they don't have symptoms doesn't mean they're going to have a pregnancy loss," Hinkle said.[3]

The study was also followed by an accompanying editorial by Siripanth Nippita, MD, and Laura E. Dodge, ScD, MPH, from the Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center. They said "This study's contribution to the existing literature is valuable for several reasons. It builds on a prior cohort study by Sapra et al and similarly enrolled a large sample of women before conception."

They further quote “The widespread availability of sensitive urine hCG tests coupled with real-time electronic data capture using mobile phone apps or similar technology has the potential to improve data quality and eliminate recall bias. Given these methodologic advantages over previous investigations, we hope that such studies can further deepen our understanding of the underlying causes of [nausea and vomiting in pregnancy]."

The researchers also urged women with nausea and vomiting in pregnancy to seek medical consultation since it negatively affects the quality of life.




[1] http://archinte.jamanetwork.com/article.aspx?articleid=2553283
[2] http://grantome.com/grant/NIH/ZIA-HD008795-08
[3] Stefanie N. Hinkle, Sunni L. Mumford, Katherine L. Grantz, Robert M. Silver, Emily M. Mitchell, Lindsey A. Sjaarda, Rose G. Radin, Neil J. Perkins, Noya Galai, Enrique F. Schisterman. Association of Nausea and Vomiting During Pregnancy With Pregnancy LossJAMA Internal Medicine, 2016; DOI: 10.1001/jamainternmed.2016.5641

Thursday, June 2, 2016

History of uterine evacuation is an independent risk factor for preterm birth: a systematic review and meta-analysis.

Preterm birth(PTB) is the birth of an infant before 37 weeks of pregnancy, according to WHO statistics an estimated 15 million babies born preterm out of whom 1 million succumb. PTB is also responsible for long term neurological complications in children like cerebral palsy, learning disabilities and visual and hearing problems.

The current global preterm birth rate is 5% to 18% and statistic shows a steady increase recently.More than 60% of preterm births occur in Africa and South Asia, India topping the list with 3 519 100 PTBs

Three forth of these births could be prevented, saving lives and money across the globe.

CDC data quotes that in the year 2014, every 1 in 10 infants was born preterm in US. For physician across the globe, PTB remains a challenge as the factors leading to preterm births are numerous, complex and not well understood. Among various contributing factors prior uterine surgery, especially those performed on cervix (induced termination of pregnancy (I-TOP) or spontaneous abortion (SAB)) has been implicated in its causation. Studies till now have shown mixed results.

The current research published in May 2016 issue of American Journal of Obstetrics and Gynecology evaluated the risk of PTB in women with a history of uterine evacuation for I-TOP or SAB.

For the data source electronic databases (MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, and Sciencedirect) were searched from their inception until January 2015. Women with prior history of uterine evacuation for either I-TOP or SAB, compared with a control group without a history of uterine evacuation were included in the study.

Total 36 case control studies involving 1,047,683 women (31 studies for I-TOP, 5 studies for SAB) met the inclusion criteria and were included in the analysis.

The primary outcome was relationship between prior evacuation and subsequent preterm births while the secondary outcome studied were low birthweight (LBW) and small for gestational age (SGA). 

Relationship between PTB and prior H/O surgical vs spontaneous evacuation was studied separately and combined both.

The study found that:

  • When all procedures combined there were increased odds of having a preterm birth, LBW and SGA babies being born after a history of surgical evacuation.
  • Vacuum evacuation and sharp curettage were associated with PTB when analyzed in combination. When analyzing separately sharp curettage was associated with higher risk.
  • Medical termination was found quite safe and did not result in PTB in subsequent surgery.
  • Women with a prior history of spontaneous abortion(SAB) have a higher risk of PTB, as compared to those with no history of SAB.
  • A very important observation as a result of meta-analysis is evacuation before 14 weeks of pregnancy (Spontaneous or induced) was not associated with increased risk for PTB.
  • Expectant management of missed abortion is an option with ending in spontaneous loss, but sometimes may end up in heavy bleeding requiring immediate evacuation.


References:











Friday, February 19, 2016

Serum Biomarkers to predict outcome in women with threatened abortion: A systemic review and diagnostic accuracy meta-analysis.




Threatened abortion approximately affect 20% of pregnancies and 50% of those will end up in miscarriage.  It has also been associated with poor obstetric outcome such as preterm labor, low lying placenta, low birth weight and PROM.

The uncertainty of prognosis makes it a challenging task for healthcare professionals.Various biomarkers have been used, with variable results to predict the prognosis of bleeding in early pregnancy.

This systemic review and meta-analysis was published in the forthcoming issue of Human Reproduction update, it aims to determine the diagnostic accuracy of various biomarkers.

A total of 19 studies were found after electronic searching of databases to determine outcomes for women with threatened abortion at 5–23 weeks gestational age.

15 studies (including 1263 women) were found eligible using QUADAS-2 (Quality Assessment for Diagnostic Accuracy Studies-2: A Revised Tool) to include in the qualitative data assessment.

The biomarkers that were looked into included serum progesterone, hCG, pregnancy associated plasma protein A, estradiol and cancer antigen 125 (CA 125).

Interestingly, serum CA 125 appeared to be the most promising marker (n = 648 women, 7 studies), whereas serum progesterone and hCG are less useful once fetal viability is established.

CA-125 is a glycoprotein and its origin is uncertain during pregnancy. It arises during the first trimester and return to a non-pregnancy range in late pregnancy.

CA 125 showed a sensitivity of 90% (95% confidence interval (CI) 83–94%), specificity of 88% (95% CI 79–93%), positive likelihood ratio of 7.86 (95% CI 4.23–14.60) and negative likelihood ratio of 0.10 (95% CI 0.06–0.20). The inverse of negative likelihood ratio was 9.31 (95% CI 5–17.1) indicating that a negative test is likely to identify those who are likely to continue with the pregnancy.

Nevertheless, when vaginal bleeding had been present for 3 days or more and there was high maternal serum CA125 activity, the abortion risk was found to be 100%.

Since this was a qualitative analysis, no cut-off value for CA125 was determined but in most studies patients who eventually aborted had values of CA-125 more than 125 IU/ml while the control had a value not more than 93 IU/ml.

A rising value of CA 125 combined with gestational sac diameter that does not correspond to the pregnancy dating is highly significant in predicting the prognosis.

Serum estradiol was the next best marker with a sensitivity of 45% (95% CI 6–90%), a specificity of 87% (95% CI 81–92%), a positive likelihood ratio of 3.72 (95% CI 1.01–13.71) and a negative likelihood ratio of 0.62 (95% CI 0.20–1.84).


References:

https://humupd.oxfordjournals.org/content/22/2/228.abstract 

https://www.researchgate.net/publication/21703609_The_prognostic_significance_of_maternal_serum_CA125_measurement_in_threatened_abortion.





http://www.ncbi.nlm.nih.gov/pubmed/12235698



Saturday, January 30, 2016

Prior First Trimester Uterine evacuation augments the risk for preterm birth in subsequent pregnancies!




Many studies have shown that a history of evacuation in women is associated with increased risk of preterm birth in subsequent pregnancy as compared to women with  no such history. But, many studies have failed to prove a direct cause and effect relationship. Other studies have linked D&C as a cause of subsequent pre term birth (PTB), but no distinction was made between surgical and medical modality of evacuation.

2 systemic reviews and meta-analysis were recently published in 2 separate journals. The first was in January, 2016 issue of Human Reproduction published on behalf of The European Society of Human Reproduction and Embryology  and the second is still in press in the forthcoming issue of  American Journal of Obstetric and Gynecology.

The Primary source of this article is the systemic review and meta-analysis in the journal of Human Reproduction, although both the analysis has concluded that Prior surgical uterine evacuation is a risk factor for subsequent pre term birth (PTB).

This is the first systematic review and meta-analysis addressing the association between D&C and preterm birth.

Since no Randomized Control Trials (RCT) were available, only cohort and case–control studies were included. A total of 21 studies reporting on 1,853,017 women were included out of that 71,231 had a history of at least one D&C in the first trimester of pregnancy. In 66,003 women, D&C had been performed for termination of pregnancy.

The control group consisted of 1,781,786 women, out of which 24. 977 women had received a medical treatment for either miscarriage or termination of pregnancy, while 1189 had had a spontaneous miscarriage and the rest were without a history of miscarriage or termination of pregnancy.

The primary outcome was a preterm delivery subsequent to an H/O curettage. The outcome of PTB was divided into 3 categories <37 weeks, <32 weeks and <28 weeks. The study also investigated a dose –response relationship by comparing women with a history of multiple D&Cs to women without a history of D&C. Many other sub-group analysis comparing   women with a D&C for miscarriage or termination of pregnancy to women with medical treatment for miscarriage or termination of pregnancy on the risk of subsequent preterm birth <37 weeks were also performed. 

The important findings of the study were:
  • It was seen that that women with a previous D&C, for miscarriage or termination of pregnancy in the first trimester, are at increased risk for preterm and especially very preterm birth, in comparison to women without a previous D&C procedure.
  • The increase in risk was statistically significant when it was only run against women who had medical management of pregnancy.
  • The risk of preterm birth increases with number of D&C performed, indicating a dose response relationship.
  • Reasonably, these findings suggest that it is the surgical management, rather than the actual miscarriage or termination, is the deciding factor about the time of delivery in the following pregnancy.

The studies included had many limitations and bias, but the strict inclusion and exclusion criteria, sensitivity and robust analysis, multiple control groups, sub-group  analysis and including prospective cohort studies  helped to limit it to certain extent. 

The mechanism by which the surgical procedure increases the risk for preterm birth remains speculative. Multiple hypotheses have been put forward such as cervical incompetence. Another theory propose a damage to  the endometrial lining which might cause abnormal placentation in a later pregnancy, thus increasing the risk of placental abruption, pre-eclampsia, placenta praevia and intrauterine growth restriction.
It is also postulated that cervical damage might impair the anti-microbial defence mechanism thereby facilitating ascending microbial colonization, a known cause of preterm births.

The clinical implications of this study are:

Frequent follow up and increase obstetrical care for women with h/o D&C, including monitoring of early signs and symptoms of threatened preterm birth.
Avoiding unneeded D&C and going more for non-invasive management options when possible i.e. expectant management or medical management in case of miscarriage, and medical management in case of termination of pregnancy.

No data is yet available on the effect of cervical priming before the D&C and subsequent risk of preterm labor. 



References:
Wieringa-de Waard M, Vos J, Bonsel GJ, Bindels PJ, Ankum WM. Management of miscarriage: a randomized controlled trial of expectant management versus surgical evacuation. Hum Reprod 2002;17:2445–2450
M. Lemmers M, Verschoor MAC, Hooker AB, Opmeer BC, Limpens J., Huirne JAF, Ankum WM, Mol BWM. Dilatation and curettage increases the risk of subsequent preterm birth: a systematic review and meta-analysis. Hum. Reprod. (2016) 31 (1): 34-
History of induced abortion as a risk factor for preterm birth in European countries: results of the EUROPOP survey Hum. Reprod. (2004) 19 (3): 734-740 first published online January 29, 200
You JH, Chung TK. Expectant, medical or surgical treatment for spontaneous abortion in first trimester of pregnancy: a cost analysis. Hum Reprod 2005;20:2873–2878
Pregnancy loss managed by cervical dilatation and curettage increases the risk of spontaneous preterm birth Hum. Reprod. (2013) 28 (12): 3197-3206 first published online September 19, 2013 doi:10.1093/humrep/det332
Shah PS, Zao J. Induced termination of pregnancy and low birthweight and preterm birth: a systematic review and meta-analyses. BJOG 2009;116:1425–1442.













Thursday, January 7, 2016

Caution in using oral fluconazole during pregnancy




Vulvo vaginal candidiasis (VVC) usually is caused by C. albicans but can occasionally be caused by other Candida sp. or yeasts as C. glabrata, C. tropicalis, C. krusei and C. parapsilosis.

Vaginal candidiasis is common during pregnancy.

According to Center for Disease control (CDC) an estimated 10-15% of women will have one episodes of Vaginal candidiasis  in pregnancy.

According to CDC 2015 Sexually Transmitted Diseases Treatment Guidelines only topical azole therapies, applied for 7 days, are recommended for use among pregnant women.

But, in cases of recurrence or severe symptoms or when topical treatment has failed oral fluconazole is often used despite of limited safety information available.

According to a recent study published in Journal of American Medical Association (JAMA) on January 5, 2016, a link is found between the use of oral Fluconozole in pregnancy and the risk of spontaneous abortion or still birth down the lane.

This is a nation wide register based cohort study by Danish researcher spanning 17 years and studying 1,405,663 pregnancies.

The pregnancies were matched on other confounding factors!

Of 3315 women who took oral fluconazole during the 7th through 22nd weeks of gestation, 147 had a spontaneous abortion. In contrast, of 13,246 matched controls (pregnant women with no fluconazole exposure), 563 had spontaneous abortions, a difference that translated into a hazard ratio (HR) of 1.48.

An increasing trend towards stillbirth was also seen in women who took oral fluconazole, when comparing with unexposed matched controls or unexposed unmatched pregnant women, but these differences were not statistically significant, reported the researcher from   the Department of Epidemiology Research at Statens Serum Institut in Copenhagen, Denmark.

A higher association was noted as the dose increased from the routine dose of 150 milligrams.

So it means that scientists concluded that women in this Danish study who used the drug during the first six months of pregnancy were almost 50 percent more likely than nonusers to have a miscarriage.

While this study does not establish a cause- effect relationship, but it does warrant larger studies, more research and a caution to physician and patient about the use of oral fluconozole in pregnancy.

Dr Scott Sullivan, a member of the ethics committee at the American Congress of Obstetricians and Gynecologists, said the new study doesn't prove any miscarriage risk from fluconazole, 'it just means we need more data, more studies'.

The researcher also urged patients in being caution taking fluconozole while pregnant as it is freely available over the counter.



References: