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In this Issue

 

MEFS 2014 joint sponsorship with Yale University School of Medecine

 

Hot topics in MEFS2014

 

Important to Know in 2015                  

  Don't edit the human germ line: Nature

  UK is about to allow mitochondrial donation  : MHR,

  Cell breakthrough to bring two-dad babies

  Live birth after uterus transplantation: THE LANCET

  SART Patient Predictor: What are my chances with ART?

  CDC Releases Final National Public Health Action Plan for the Detection, Prevention and Management of Infertility

 

Important to learn in 2015

BEST OF ESHRE & ASRM 2015: an emphasis on transatlantic debate.

In this meeting, held in New York, with more than 900 participants, the following topics were highlighted from European and American sides

ART results in the USA are ‘better’ than in Europe?

The ability of PGS to improve live birth

Is time-lapse imaging proposed as ‘superior to classical morphology’ for embryo selection?.

The treatment of unexplained infertility.

The best treatment for women with diminished ovarian reserve

Ovarian tissue transplantation

Mitochondrial donation and replacement.

 

 

Member Societies and readers are invited to send all comments, reports or articles to

Middle East Fertility Society

Achrafieh, P.O.Box :167220

Beirut, Lebanon

Phone: + 961-1-610400

Fax: + 961-1-612400

news@mefs.org

 

From the Editor

The Middle East Fertility Society is the primary organization of professionals dedicated to expanding the knowledge of assisted reproduction in Middle East.  MEFS’s mission has been always set to help maintaining the standards for ART, in an effort to better serve its members and their patients.

The last meeting in Abu Dhabi on September 25-27, 2014 had witnessed more than 70 oral presentations, given by about 55 renowned international and regional speakers. This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of YALE University School of Medicine and Middle East Fertility Society.

MEFS Society advocates for quality and maintains the highest standards of continuing education. The Society has been always keen to organize pre-congress courses and symposia in annual meetings of ASRM and ESHRE. And, having the highest scores from these courses attendants does indeed reflect the enormous amount of work done in our society.

MEFS firmly believes that science must be at the core of our life. Our journal supports guaranteed access to the full array of abstracts and full text studies. Our mission of transferring medical knowledge and promoting scientific research are increasingly reflected in the higher quality of published studies.

 

We are always looking for further expansion and nonstop improvement. We hope to see you all, our valued partners, in the next 22nd annual meeting in Sharm El Sheikh, November 5-7, 2015.

 

Eman Elgindy MD, PhD

Editor

 

 

MEFS 2014 joint sponsorship with YALE University School of Medicine (Great Event)

MEFS 2014 scientific event was a joint sponsorship between MEFS and YALE University School of Medicine. This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME). YALE University School of Medicine is accredited by the ACCME to provide continuing medical education for physicians

In order to maximize the learning experience of participants, an interesting problem-solving and evidence-based format was designed for the official MEFS 2014 presentation as follow:

Section 1. Topic’s title; Speaker’s name, titles, affiliations, Conflicts of interest declaration.

Section 2. Learning Objectives.

Section 3. Presentation of a ‘Clinical Case’. [A typical clinical scenario representing a dilemma encountered in daily clinical practice]

Section 4. Presentation of the Scientific Evidence and/or Research Findings.

Section 5. Brief discussion of the ‘Clinical case’ in view of the body of information presented.

Section 6. Take-home messages. [Clear and concise, while specifying the Strength of Evidence for each message whenever possible]

The abovementioned method of MEFS 2014 presentations have been addressed in the most important topics of reproductive medicine. Updated Reproductive endocrinology, recent trends in ovarian stimulation for ART, Prediction and up to date management of poor ovarian response as well as the most updated knowledge about PCOS and endometriosis were presented by imminent international speakers. The conference also included sessions emphasizing on recent trends in embryology, male factor infertility, implantation, optimal luteal phase and various modalities of improving ART outcome. Nevertheless, menopause and psychology sessions were also included in our program with large number of attendants.

Indeed, we received highly positive feedback from all our participants. Furthermore, in order to enhance long-term retention of knowledge, a Remote Knowledge Center (RKC) has been created to provide participants with periodic e-mail reminders of Take-home Messages and Acquired Concepts.


 

 

Hot Topics in MEFS 2014  

 

  I ) Plenary Session

PERSONAL GROWTH:  TRAIN YOUR BRAIN to thrive from nine to five

Johnny Awwad (Lebanon): Multitask is destructive to our brain:

 

Mitochondrial nutrients to energize old eggs

Robert Casper (Canada)

 

 

II) Controversial subjects in MEFS 2014

 

PGS: where we are now?   Elevated progesterone and progesterone/estradiol ratio on day of HCG  
  PGS: are easy, accurate and applicable    PGS: not yet for clinical application They have detrimental effect on pregnancy   They have no detrimental effect  
Preimplantation Genetics: Techniques and technology made easy  - Chantal Farra (Lebanon)    Preimplantation genetic screening (PGS), still in search of a clinical application Norbert Gleisher (USA)  

Elevated progesterone and/or elevated progesterone/estradiol ratio on the day of hCG: which is more detrimental?   Eman Elgindy (Egypt)

 

 

  High progesterone is a myth Peter Humaidan

 

 

 
PGS using Comprehensive Chromosome screening: achievements and challenges Elias Dahdouh (Canada)        
             

 

         

 

 

 


 

    Important to Know in 2015

 

  Don't edit the human germ line: Nature

(Mar 12, 2015: volume 519: Number (7544) P 410-1)

Edward Lanphier and colleagues reported that, the use of current technologies for genome editing of human embryos could have unpredictable effects on future generations .They highly questioned the ethical and safety implications of this research. They stated that “Heritable human genetic modifications pose serious risks, and the therapeutic benefits are tenuous”

 

 

 

 

 

 

 

 

 

Live birth after uterus transplantation: THE LANCET

(Feb 14, 2015: Volume 385: Number 9968 p577-662)

a 35-year-old woman with congenital absence of the uterus, underwent transplantation of uterus in Sahlgrenska University, Gothenburg, Sweden. The uterus was donated from a living, 61-year-old, two-parous woman. IVF of recipient and her partner was done before transplantation and 11 embryos were cryopreserved. One year after transplantation, the recipient underwent her first single embryo transfer, which resulted in pregnancy.   The patient had pre-eclampsia at 31 weeks and 5 days. A caesarean section was done 16 h later because of abnormal cardiotocography. A male baby was born, with a normal birth weight for gestational age (1775 g) and with APGAR scores 9, 9, 10.

 

   
 

UK is about to allow mitochondrial donation  : MHR,

March 2015, Volume 21 Issue 3

UK's lower Parliament (the House of Commons) had approved mitochondrial donation in couples known to be at high risk of passing on mitochondrial diseases to their children. If this succeeds in passing the House of Lords and meet the requirements of the HFEA, the first trials could begin towards the end of this year. These trials are mostly at Newcastle University, under direction of Professor Doug Turnbull.

 

SART Patient Predictor: What are my chances with ART? SARTCORS Online

 SART has developed this predictor based on nearly 500,000 cycles of therapy to more than 320,000 women throughout the United States since 2006. This calculator is meant to help understand the chances of having a live birth, based on personal situation. It is based on, age, height, weight, prior pregnancies, prior full term and Diagnosis of infertility.

 

   

  Cell breakthrough to bring two-dad babies, THE SUNDAY TIMES February 22, 2015

     For the first time, it is possible to make human egg and sperm cells using skin from two adults of the same sex. The breakthrough, funded by the Wellcome Trust, was achieved at Cambridge University in a project with Israel’s Weizmann Institute of Science.

The scientists used stem cell lines from embryos as well as from the skin of five different adults. Researchers have previously created live baby mice using engineered eggs and sperm, but until now have struggled to create a human version of these “primordial germ” or stem cells.

A gene called SOX17, previously considered to be unimportant in mice, was turned out to be critical in the process of “reprogramming” human cells.

“We have succeeded in the first and most important step of this process, which is to show we can make these very early human stem cells in a dish,” said Azim Surani, professor of physiology and reproduction at Cambridge, who heads the project. Interestingly, Prof Surani was involved in research that led to the birth of Louise Brown, the world’s first test-tube baby, in 1978.

The Nobel prize winner Professor Sir Martin Evans, who was the first to produce embryonic stem cells from mice, said the research gave “a new explanation of one [element] of human biology . . . but until it is applied for a practical purpose it is only a small incremental step”.

 

CDC Releases Final National Public Health Action Plan for the Detection, Prevention and Management of Infertility 

The National Action Plan is available at www.cdc.gov/reproductivehealth/Infertility/PublicHealth.htm.

In consultation with many governmental and nongovernmental partners, the Centers for Disease Control and Prevention (CDC) developed the National Public Health Action Plan for the Detection, Prevention, and Management of Infertility ( called the National Action Plan or the Plan). This plan highlights the need to better understand and address issues at a population level that contribute to and are caused by infertility in women and men and that may affect the health of the pregnancy.

Specifically, this plan focuses on:

1.    Promoting healthy behaviors that can help maintain and preserve fertility.

2.    Promoting prevention, early detection, and treatment of medical conditions that can threaten fertility.

3.    Reducing exposures to environmental, occupational, infectious, and iatrogenic agents that can threaten fertility.

 

 

 

-        


 

 

Important to learn in 2015

BEST OF ESHRE & ASRM 2015: an emphasis on transatlantic ‘debate’

 

In this meeting, held in New York, with more than 900 participants, the following topics were highlighted from European and American sides

 

ART results in the USA are ‘better’ than in Europe ?

The ability of PGS to improve live birth

Is time-lapse imaging proposed as ‘superior to classical morphology’ for embryo selection?.

The treatment of unexplained infertility.

The best treatment for women with diminished ovarian reserve:

Ovarian tissue transplantation

Mitochondrial donation and replacement.

 

 

 

 

ART results in the USA are ‘better’ than in Europe?

 

Glenn Schattman from Weill Cornell Medical College in New York: Evidence from the database of SART and a few multicentre trials, had shown:

1-     Better outcomes in the US centres than in the European. Live birth rate in the US centres of one such trial was 38.2%, while in European centres 27.6%.

2-      More oocytes and better quality embryos in US centers.

 

Dr Schattman proposed ‘the quality of care may be different’ in screening and in the lab. ‘Every step is better,’ he said, and especially in paradigm of the fresh original cycle.

 

Bart Fauser from Utrecht University in the Netherlands, challenged this,,,,,, He said “ this is the wrong Paradigm”. And, results should not only include LBR, but also multiple pregnancies, safety and cost.

 

Fauser’s definition for optimizing IVF outcome was that “it should be effective as measured by delivery of a healthy baby over a definitive course of time, safe in terms of multiplicity and complications to mother and baby, and cost effective when indicative of broad access to treatment”.

 

He proposed that such parameters should replace any dependence on oocyte number, embryo number, implantation rate and pregnancy rate (PR)/ cycle or PR/transfer as markers of ‘successes.

 

 

 

The ability of PGS to improve live birth

 

William Schoolcraft, from Colorado, proposed that the comprehensive chromosome screening (CCS) of embryos  is of genuine benefit in IVF. The following were stated

1-     Screening embryos by FISH for a limited number of chromosomes had been disappointing. And ‘that’s history.’

2-      Combination of trophectoderm biopsy, blastocyst vitrification, and single-nucleotide polymorphism (SNP) array technology for (CCS) does indeed result in high implantation and live birth rates. This will help practical application of single embryo transfer. Now, the technology is moving on to next generation sequencing. Schoolcraft noted that blastocyst biopsy ‘has many advantages’. He mentioned a recent systematic review of blastocyst biopsy for CCS (compared with routine IVF) which found higher IR and OPR in CCS group, when the same number of embryos is transferred. Therefore, this will improve embryo selection for SET and sharply decrease multiple rates.

  

Sjoerd Repping, the Amsterdam biologist, questioned this topic and said ‘Can PGS improve live birth rates?’ he asked? And replied ‘It never will.’ While FISH is considered a history, PGS has entered its second phase with a shift to polar body or blastocyst cell analysis and array CGH. Repping, however emphasized that most of the trials supporting these second phase technologies are flawed. For example, the study of Scott et al of 2013 (an RCT of blastocyst biopsy with CCS) was criticised by Repping as only in good prognosis patients, with randomization on day 5, and with all subjects progressing to transfer.

Repping suggested that these ‘potentially risky reproductive technologies’ should remain the subject of research until after preclinical investigation, clinical trials and follow-up studies.

 

 

 

Is time-lapse imaging proposed as ‘superior to classical morphology’ for embryo selection?.

Giovanni Coticchio, from Monza, Italy was the proponent of this new technology. He proposed that imaging can detect aberrations in the embryo which morphology cannot do - notably ‘reverse cleavage’ and multinucleation. His evidence came from the RCT of Rubio and colleagues at IVI in Spain, published in Fertility and Sterility in November 2014. The study included 843 patients and embryo development was assessed by morphology or the time-lapse system. There was a higher OPR in the time-lapse group (51% vs 41% per treated cycle) as well as lower pregnancy loss and higher implantation rates.

 

Interestingly, Coticchio himself asked, whether the better results achieved by time-lapse imaging itself, or by the better culture and observation conditions?

 Catherine Racowski, from Harvard Medical School was unable to find an answer in the available evidence - including the IVI trial. Dr Racowski stated that ‘I believe we are still in the development/calibration phase,’ She enumerated the following limitations

1- The majority of studies are retrospective (though not Rubio et al) and heterogeneous in their design.

2- She criticized the IVI trial design, as 30 of the patients randomized to morphology were placed on request in the time-lapse group. Further, the study had a high risk of bias for selection, selective reporting as well as performance, specially that different incubators were used for the two groups.

3- None of the available studies reported increased live birth rate, which is the optimal endpoint.

 

 

The treatment of unexplained infertility.

 

Owen Davies, from Weill Cornell Medical College in New York favoured the ‘expedited’ approach. A quick recourse to IVF would, reduce risk of multiples and provide better opportunity of embryo selection and SET. And, he emphasized that stimulation with a GnRH antagonist will decrease OHSS. He counted on results of the 2010 FASTT trial in which an accelerated protocol (three IUI cycles and immediate IVF) was compared with a standard protocol of clomiphene- and later FSH-stimulated IUI followed by IVF. Higher pregnancy rate, lower time to pregnancy and lower cost were reported in the accelerated approach.

 

Roy Homburg, was more equivocal in highlighting the place of IVF in unexplained infertility. He reported that

1-  About one-third of couples will conceive within three years without treatment (and 30% within a year).

2-  Treatment outcome depends upon prognosis, which is mainly determined by female age and duration of infertility.

3-  Recent studies found no difference in live birth rates between IVF and IUI. Dr Homburg questioned the value of the 2012 NICE recommendation, which recommended expectant treatment for up to two years and then IVF.

4-  A more accurate answer to this question may arise from a RCT now in progress with Homburg’s own group - 280 couples randomized to three cycles stimulated IUI or one cycle IVF.

 

 

 

 The best treatment for women with diminished ovarian reserve:

 

- Frank Broekmans, from Utrecht and Marcelle Cedars from San Francisco had considerable agreement.

There is no single stimulation protocol, which would suit all cases, and increasing FSH doses have little effect.

 

 Broekmans suggested that ‘it’s all about female age . . . the cohort, not the FSH dose’ (or any of the proposed adjuvant treatments).

 

 

 

 

Ovarian tissue transplantation

Kutluk Oktay, formerly of Europe and now of New York Medical College, reported the birth of about 40 babies after ovarian transplantation. Two strategies to improve ovarian transplant revascularization were presented:

1- The use of agents (such as S1P) to accelerate the process.

2- Enhanced surgical techniques, specialy robotically assisted. Oktay announced  that the technique had produced its first pregnancy. ‘Now,’ said Oktay, ‘we have the chance to do a more delicate job.’

 

 

 

Mitochondrial donation and replacement.

 

Mary Herbert, from the Newcastle, UK, is the first in the world to begin clinical trials following approvals in both houses of the UK parliament. She discussed the following

1-     Mutations in mitochondrial DNA affect energy production and thereby have serious consequences for organs requiring a lot of energy (such as the heart or brain).

2-     Prevalence of mitochondrial disease is around one in 5000, with debilitating and fatal consequences. In cases of high mutation load- with procedures as PGD are not indicated - two nuclear DNA transfer techniques are investigated in Newcastle, meiotic spindle transfer and pronuclear transfer. There are two principal considerations in each: the onward development of the embryo and the reduction in mutation load sufficient to prevent disease.

 

Both principles have been done in mouse models, and now, the work can progress to human zygotes.

 

 

The steering committee of the meeting announced that the annual schedule will now be extended to every two years, with the next event planned for Europe in 2017.