COGI 2018: 5 key messages

COGI is over for another year. Now we can take time to digest the information from the inspiring and thought-provoking sessions and ask ourselves: ‘what have we learnt?’

In this special edition blog we look back at five key messages and highlights from the three days.

 

1.       Time to consider HRT for primary CHD?

Research suggests that estrogen has a clear biological effect on the cardiovascular system, demonstrating beneficial effects on some of the key risk factors of Cardiovascular Heart Disease (CHD). While there is a lack of definitive evidence supporting HRT as a prevention for postmenopausal CHD, there are a growing number of epidemiological and observational studies supporting its use. In these studies, timing was shown to be a key factor with HRT demonstrating no benefit in older women. However, although there was no benefit there was also no evidence of harm.

 

2.       The role of epigenetics in long term health

Specific epigenetic input during development can produce a lasting difference in phenotype, meaning fetal programming, metabolic endocrine disruption and structural change in organs can all significantly affect the birth of a child.

For example, Caesarean Sections are linked to increases in neonatal morbidity, auto-immune diseases and metabolic disease in the offspring. Maternal obesity and smoking are also shown to be associated with long term negative outcomes for the child. In fact, research suggests that these negative effects may even cross generations.

 

3.       Fertility may be able to be preserved in women with POI

Primary ovarian insufficiency (POI) affects 1 in 100 women at the age of 40. In order to plan the most effective fertility preservation treatment, it is crucial to predict as much as possible whether POI may be imminent. While this is not simple, the condition is hereditary therefore assessing family history may help to provide important insight. Additionally, more research is taking place into the genetic basis of POI, with some evidence suggesting that reproductive health and success may be a marker for identifying POI and health outcomes later in life.  

There are many more options available for treating imminent POI than confirmed POI, including vitrification of oocytes or embryos following ovarian stimulation, freezing of ovarian tissue or a combination of the two. When treating confirmed POI, the options are more complex. While a small number of sufferers may go on to experience a spontaneous pregnancy, researchers are now considering a new technique: in vitro follicle activation (IVA). However, refinement and improvement of the technique is needed for it to lead to an effective strategy for these patients.

  

4.       The freezing debate is definitely not over!

The debate on whether freezing oocytes for non-medicinal reasons is truly beneficial contined at COGI. Speakers argued that social freezing could be seen as a purely commercial enterprise with advertising often aggressive and marred with misinformation. In fact, only 12% women actually return to the clinic and there is a far from certain chance of success.

However, freezing was shown to provide effective results in younger women seeing fertility preservation. In addition, some studies have demonstrated that freezing may be able to reduce risk of OHSS and be beneficial for groups of high responders.

 

5.       ART may be driving rates of pre-term birth

ART is associated with increased incidence of multiple pregnancy. Multiple pregnancy in turn is related with higher risk of pre-term birth and Cerebral Palsy. Using real world data we were shown that incidence of twins born at <32 weeks increased 27-fold from 1987 to 2010, with ART suggested as a main driver.

ART and preterm birth - What is the link?

Preterm birth is associated with a number of adverse health conditions contributing to increased rates of infant mortality, morbidity and long-term disability.[1] For example, 3-4% of very preterm and very low birth weight babies have Cerebral Palsy. [2]

Speaking at COGI 2018, Prof. Andrew Shennan explained that the issue is considerable, costing the NHS around £1 billion a year.  To be able to effectively tackle the problem, we must understand the key causal factors along with developing and improving management and prevention techniques.

 

Is ART driving premature pregnancy?

The link between ART and increased incidence of multiple pregnancy is well established.[3] In 2014, data from the Centers for Disease Control and Prevention (CDC) indicated that over 20% of all births following ART were multiple births.

Also established is the understanding that multiple pregnancy can result in higher rates of mortality and morbidity both for the mother and child.[2] One of the key complications resulting from multiple pregnancy is pre-term birth. In a thought-provoking session, Prof. Isaac Blickstein discussed why we therefore must consider the major impact that ART could be having on rates of premature pregnancy.

Using mathematical analysis of current preterm and Cerebral Palsy population statistics, Prof. Blickstein demonstrated that out of 100,000 spontaneous births, 2000 twins would be expected, of which 1685 would be very premature and 59 would have Cerebral Palsy.  In contrast, just 10,000 births by ART would be expected to produce 7400 twins, 740 very premature births and 26 cases of Cerebral Palsy.

But how about using real world data? Well, sharing data from a recent population trial, Prof. Blickstein indicated that the incidence of twins after ART born at <32 weeks increased 27-fold from 1987 to 2010 and has not reduced from the peak incidence in the last decade. He suggested that this high level of multiple pregnancy is a key driver of the issue of pre-term birth that we see today.  

 

Managing preterm birth

The speakers agreed that unfortunately there is no clear and definitive strategy to manage pre-term birth, especially in regards to multiple pregnancy. It was discussed that short cervical length is clearly associated with preterm labour and can be used in predicting and preparing for prophylactic intervention. These include:

-          Progesterone

o   While progesterone has been shown to be effective in singleton birth, it has not in multiple pregnancy, even if the delivery is high risk.[4]

-          Cervical Pessary

o   There is no clear evidence to the benefit of the cervical pessary, with some supporting studies and some suggesting no benefit at all.

o   However, Prof. Ben Mol discussed that the treatment could be effective for patients that have a short cervix (25-30mm). He recommended that it may especially be useful for women with multiple pregnancy, as progesterone is not shown to be effective.

-          Cerclage

o   Cerclage needs to be further researched in modern randomised controlled trials. However, Prof. Shennan explained that it could be beneficial in high risk cases.

o   Abdominal cerclage was not recommended as a first line treatment however could be effective for women who had a failed vaginal cerclage.

-          Lifestyle factors

o   Smoking and obesity were outlined as factors increasing risk of complication.

In the UK, Public Health England have announced they will aim to reduce preterm birth to 6% by 2025. While this may not necessarily be reached, it hopefully means that there will be budget available to help future research.


Sources:

[1] Keelan JA, Newnham JP. Recent advances in the prevention of preterm birth. F1000Res. 2017;6:F1000 Faculty Rev-1139. Published 2017 Jul 18. doi:10.12688/f1000research.11385.1

 [2] Kim Van Naarden Braun, Nancy Doernberg, Laura Schieve, et al. Birth Prevalence of Cerebral Palsy: A Population-Based Study. Pediatrics. Jan 2016, 137 (1) e20152872; DOI: 10.1542/peds.2015-2872

 [3] Multiple pregnancies following assisted reproductive technologies – A happy consequence or double trouble? Seminars in Fetal and Neonatal Medicine, 19(4), 222-227, 2014 doi: https://doi.org/10.1016/j.siny.2014.03.001

 [4] Klein, K. , Rode, L. , Nicolaides, K. H., Krampl‐Bettelheim, E. , Tabor, A. and , (2011), Vaginal micronized progesterone and risk of preterm delivery in high‐risk twin pregnancies: secondary analysis of a placebo‐controlled randomized trial and meta‐analysis. Ultrasound Obstet Gynecol, 38: 281-287. doi:10.1002/uog.9092