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.

Fertility preservation in women with POI

Primary ovarian insufficiency (POI) is a clinical syndrome defined by loss of ovarian activity before the age of 40 years. It is also known by the term premature menopause and can be characterised by menstrual disturbance with raised gonadotropins and low estradiol. While incidence of POI depends on ethnicity, generally the risk is 1 in 1000 at age 30 and 1 in 100 at age 40.

The consequences of POI are unfortunately long term and severe including:

-          Cognitive dysfunction

-          Cardiovascular Disease

-          Autoimmune diseases

-          Osteoporosis

-          Increased mortality

-          Infertility

Presenting on the final day of COGI 2018, Prof. Claus Andersen explained that there is a key focus on providing women with POI the option of fertility preservation. So, what are the available treatments?

 

Approaches for fertility preservation

In order to plan the most effective fertility preservation treatment, Prof. Andersen stressed that it is important to predict as much as possible whether POI may be imminent. How can we do this? Well, often the condition is hereditary. In fact, Prof. Andersen suggested that around 10-15% of women with POI would have a first degree relative who has been affected. Similarly, if a woman has a mother or older sister affected this leads to an approximately 6x higher risk.

There are many more available options for treating women with imminent POI than confirmed POI. Therefore, it is essential women are informed about symptoms and risks. It is also essential that health care professionals understand this increased risk and consider it when diagnosing a potential case.

At COGI we were shown data suggesting that a quarter of women waited over five years for a correct diagnosis, with over half seeing more than three clinicians.  Unfortunately, there is no definitive test for predicting POI, however we can hope that this could be developed in future.

 

Imminent POI

For women with imminent POI, Prof. Andersen discussed three main first line approaches:

-          Vitrification of oocytes or embryos following ovarian stimulation

-          Freezing ovarian tissue

-          A combination of oocyte and ovarian tissue freezing

 

Confirmed POI

For those with confirmed POI, treatment is more complex. In some cases, sufferers may experience spontaneous pregnancy. One study of 358 women revealed that a cumulative pregnancy rate of 4.3% at 48 months.[1]

However the alternative is a procedure called in vitro follicle activation (IVA). This involves the removal of an ovary, the preparation of cortical tissue recruiting dormant primordial follicles, freezing and thawing before transplantation back into the POI sufferer. Research is still be undertaken into IVA. However, with refinement and improvement it could lead to a new effective strategy for POI patients to conceive their own genetic children.[2]  


Sources:

[1] M. Bidet, A. Bachelot, E. Bissauge et al. Resumption of Ovarian Function and Pregnancies in 358 Patients With Premature Ovarian Failure. Obstetrical & Gynecological Survey: 2012. 67(4). 231–232. doi: 10.1097/OGX.0b013e3182502238

[2] Kawamura K, Kawamura N, Hsueh AJ. Activation of dormant follicles: a new treatment for premature ovarian failure?. Curr Opin Obstet Gynecol. 2016;28(3):217-22.

The freeze all debate: an introduction

Despite IVF technology evolving significantly over the last 40 years, the process is far from perfect. Current research is still incredibly important to study how we can improve live birth rates, patient safety and reduce the time to live birth. [1]

One area of particular debate is whether a freeze all or fresh transfer approach is preferable when transferring embryos. But what is a freeze all approach and why is this discussion important?

What is a freeze all approach?

Following oocyte stimulation, retrieval and oocyte fertilisation, two options for embryo transfer are available. During a fresh embryo transfer a selected embryo can be transferred back to the mother soon after oocyte retrieval. Alternatively, the embryos can be vitrified and stored for transfer later. This is also called the “freeze all” approach, where embryos are then thawed before transfer.[1] 

The freeze all method was initially developed for the purpose of fertility preservation, such as for patients due to undergo chemotherapy. However, there is evidence that it may be a preferred option for all fertility patients. This is in light of data suggesting that staggering oocyte stimulation and embryo transfer allows the endometrium to be better primed for receipt of an oocyte.[2] There is also evidence that it can lessen the risk of ovarian hyperstimulation syndrome (OHSS).[1]

 

Effect of the freeze all method on outcomes in pregnancy, birth and neonate health

A 2014 retrospective cohort study, the largest of its kind, concluded that the use of vitrified thawed embryos did not worsen the outcomes in respect to pregnancy, birth and neonate health in comparison to the use of fresh embryos. The only notable differences were a greater number of interventions and a lower number of urinary tract infections reported with the vitrified oocyte group compared to the fresh oocyte group.[3]

 Further data from the Society for Assisted Reproductive Technology in 2011, found that gestational carriers receiving frozen-thawed embryos had 7-8% higher age-adjusted success rates than non-gestational carrier comparators receiving fresh embryos.[2]

 

The programmed endometrium 

There is evidence to suggest that ovarian stimulation can cause irregular endocrine milieu which could hinder embryo implantation during a fresh IVF cycle. Whereas, the freeze all method allows thawed embryos to be transferred at later cycles when the endometrium is programmed to be more receptive to freeze-thawed embryos.[1]

 

Risk of OHSS

There is evidence that the risk of developing OHSS is greater during fresh IVF cycles as oocyte development, retrieval and embryo transfer occur around the same time. It has been suggested that staggering oocyte stimulation by using the freeze all method could reduce this risk. Robust randomised controlled trials are underway to determine if the freeze-all method could lessen the risk of OHSS without reducing successful treatment outcomes.[1]

 

The debate continues at COGI

The World Congress on Controversies in Obstetrics, Gynecology & Infertility (COGI) congress will be held in London on 23rd-25th November, with key discussions including a debate on social freezing and a presentation titled ‘the end of freeze all?’. We will be attending to provide you with the latest updates from the conference, including research highlights and key messages.

Sources:

1.       Niederberger, C., Pellicer, A. and Cohen, J. et al. Forty years of IVF. Fertil Steril. 2018; 110 (2), 185-324.

2.       Society for Assisted Reproductive Technology. 2010 and 2011 SART fertility success rate report. Available at: http://www.sart.org/SART_Success_Rates.

3.       Cabo, A., Serra, V., Garrido, N. et al., Obstetric and perinatal outcome of babies born from vitrified oocytes. Fertil Steril. 2014; 102 (4), 1006-1015.