Previous highlights 2018

Highlight December 2018

Human Reproduction’s greatest hits: My personal top-10 of 6 years as a Human Reproduction editor - Human Repr (33)12; 2159–2161;

I’m at the end of my term as Editor-in-Chief of Human Reproduction. To appreciate how much I have enjoyed being an editor, please read my last Editorial (Evers, 2018). I salute you.

Highlight November 2018

Y Ikemoto, K Kuroda, A Ochiai, S Yamashita, S Ikuma, S Nojiri, A Itakura, S Takeda

Prevalence and risk factors of zygotic splitting after 937 848 single embryo transfer cycles - Human Repr (33)11; 1985-1991;

1.36% zygote splitting after nearly one million single embryo transfers
In 2008, as one of the first in the world, the Japanese Society of Obstetrics and Gynaecology officially recommended the adoption of SET to reduce multiple pregnancies. This allowed Yuko Ikemoto and co-workers ten years later to investigate the outcome of no less than 937,848 SETs, in what I predict will become a landmark study.
Fresh and frozen-warmed SET produced 276,934 clinical pregnancies (29.5%/SET), including 4,310 twins (1.56% of pregnancies) and 109 triplets (0.04% of pregnancies). The prevalence of multiple pregnancies with zygote splitting was 1.36%. Compared to singleton pregnancies, zygote-splitting pregnancies were more frequently associated with frozen-warmed ET cycles, blastocyst culture, and assisted hatching.

Highlight October 2018

K E Liu M Hartman A Hartman Z -C Luo N Mahutte

The impact of a thin endometrial lining on fresh and frozen–thaw IVF outcomes: an analysis of over 40 000 embryo transfers - Human Repr (33)10; 1883–1888;

More than 1200 embryo transfers with an endometrial thickness below 7mm
The impact of a thin endometrium has been a longstanding topic of lively debate among IVF clinicians. Kimberly Liu et al., from Toronto, Canada, now have reviewed over 40,000 fresh and frozen IVF cycles. They show that live birth rates decreased and pregnancy loss rates increased with each millimeter decline of endometrial thickness below 8 mm in fresh transfer cycles. In frozen transfer cycles, live birth rates decreased below 7mm, but no significant difference in pregnancy loss rates was found. The likelihood of achieving an endometrial thickness over 8 mm decreased with age. Yet, live birth rates remained fair (15-21%) in patients with an endometrial thickness of 5-6 mm in fresh and 4-6 mm in frozen cycles. Data were ‘suppressed and not available’ for 49 embryo transfers in women with an endometrium below 4 mm.

Highlight September 2018

Willem Verpoest Catherine Staessen Patrick M Bossuyt Veerle Goossens Gheona Altarescu Maryse Bonduelle Martha Devesa Talia Eldar-Geva Luca Gianaroli Georg Griesinger Georgia Kakourou Georgia Kokkali Jana Liebenthron Maria-Cristina Magli Monica Parriego Andreas G Schmutzler Monica Tobler Katrin van der Ven Joep Geraedts Karen Sermon

Preimplantation genetic testing for aneuploidy by microarray analysis of polar bodies in advanced maternal age: a randomized clinical tria - Human Repr (33)9; 1767-1776;

Esteem, verb trans: to regard with respect and admiration
And here it finally is, the much anticipated ESTEEM trial. After all the usual wear and tear (and more) of doing a randomized clinical trial (RCT) at 9 sites in 7 countries, lagging recruitment, power failure, increased costs, attrition, protocol violations, drop-outs, lost to follow-up, the trial landed on our pages. It illustrates why people are reluctant to do RCTs. They last long, cost much and produce results when the ART field has hurried ahead already to new sensational developments. But we need them, someone has to do the leg work. Joep Geraedts, Karen Sermon, Willem Verpoest and their 29 collaborators in ESTEEM provide the evidence that preimplantation genetic testing for aneuploidy (by comprehensive chromosome screening of the first and second polar body to select euploid embryos for transfer) does not substantially increase the live birth rate following ICSI in women aged 36 to 40 years.


Highlight August 2018

Annika Ramin-Wright Alexandra Sabrina Kohl Schwartz Kirsten Geraedts Martina Rauchfuss Monika Martina Wölfler Felix Haeberlin Stephanie von Orelli Markus Eberhard Bruno Imthurn Patrick Imesch Daniel Fink Brigitte Leeners

Fatigue – a symptom in endometriosis; Human Reprod (2018) 33 (8): 1459–1465,

Fatigue and endometriosis
In this month’s Human Reproduction, Annika Ramin-Wright and the group of Brigitte Leeners from Zürich point out that fatigue is an underestimated symptom in endometriosis. They suggest that to improve the quality of life in women with endometriosis, addressing fatigue should become a part of medical care. According to these clinical investigators, reducing insomnia, pain, depression, and occupational stress would allow for better managing fatigue in patients with endometriosis.

Highlight July 2018

Richard A Anderson David H Brewster Rachael Wood Sian Nowell Colin Fischbacher Tom W Kelsey W Hamish B Wallace

The impact of cancer on subsequent chance of pregnancy: a population-based analysis; Human Reprod (2018) 33 (7): 1281–1290,

Fertility after cancer, these are promising times

We publish a record six papers on reproductive epidemiology this month. I selected one.
In Scotland, like in Scandinavia, linkage of national databases offers the opportunity to study whether women achieve pregnancy after a cancer diagnosis on a population basis. Richard Anderson and co-workers made use of this. They show that nowadays cancer has less negative impact on the chance of a subsequent pregnancy in young women than 20-30 years ago. This goes for some key cancers like cervical cancer, breast cancer and Hodgkin lymphoma. There has however not been an improvement in the impact of other cancers, notably leukaemia and brain/CNS cancer. These data quantify the impact of cancer on the chance of becoming pregnant. They highlight the need for interventions to protect fertility in girls and young women with cancer, and to support them if they consider pregnancy once their treatment is completed.

Highlight June 2018

D Van Saen V Vloeberghs I Gies I Mateizel K Sermon Jean De Schepper H Tournaye E Goossens

When does germ cell loss and fibrosis occur in patients with Klinefelter syndrome? - Hum Reprod (2018) 33 (6): 1009–1022,

Klinefelter patients lose germ cells earlier than we thought

Will fertility preservation techniques improve the chances of young Klinefelter patients to reproduce as an adult? When do their germ cells disappear? In Klinefelter syndrome, germ cell loss is not observed in fetal testicular tissue in the 2nd semester of pregnancy. It is manifest however at a prepubertal age when the testicular architecture is still normal. Germ cells are lost at a very young age, even before initiation of the fibrotic process. Fibrosis is exceedingly present at an adolescent age. At an early adolescent age, sperm recovery, e.g. by TESE, has a poor outcome, as poor as in adult Klinefelter patients. This was shown by Dorien van Saen and co-workers, from Brussels, Belgium, who conclude that preventive testicular stem cell banking remains questionable. They discourage fertility preservation attempts in boys with Klinefelter syndrome outside a proper research framework.

Highlight May 2018

Qianqian Zhu Qiuju Chen Li Wang Xuefeng Lu Qifeng Lyu Yun Wang Yanping Kuang

Live birth rates in the first complete IVF cycle among 20 687 women using a freeze-all strategy - Hum Reprod (2018) 33 (5): 924-929,

Freeze-all: 51% live births in first cycle

What is the chance of having a child following one complete in vitro fertilization (IVF) cycle for patients using a freeze-all strategy? This is the question that Qianqian Zhu and co-workers from Shanghai, China, asked themselves. The answer, after doing 20,687 freeze-all cycles, is that the chance of having a child after one complete freeze all cycle and all resulting embryo transfers is 51%.

Highlight April 2018

Tessa J Roseboom

Developmental plasticity and its relevance to assisted human reproduction - Human Reproduction, Volume 33, Issue 4, 1 April 2018, Pages 546–552

Developmental plasticity: an outside expert’s look at ART practices

The importance of developmental plasticity for human health was highlighted by David Barker (of the ‘Barker hypothesis’), who suggested that foetal adaptations to environmental cues might be the cause of health disturbances later in life. We recently have started to appreciate that even before the foetal period, embryonic exposure to ‘environmental cues’ may also affect later life. My Editor’s choice for this issue is a truly thought provoking paper, “Developmental plasticity and its relevance to assisted human reproduction” by Professor Tessa Roseboom. It was literally an Editor’s ‘choice’, I invited her to update us on developmental plasticity, and she agreed. Tessa Roseboom is world famous for her groundbreaking work on the developmental consequences of being prenatally exposed to famine in the Dutch hunger winter of 1944-1945. Who better to look from the outside at our daily ART practices, with all its ‘environmental cues’ to the early pre-implantation embryo?

Highlight February 2018

O Basso;C R Weinberg;A A D’Aloisio;D P Sandler - Maternal age at birth and daughters’ subsequent childlessness - Human Reprod (2018) 33 (2): 311–319, 


Older mothers, big data and childless daughters

The older a woman is when she conceives, the more likely her progeny – if a daughter – is to remain childless. As this is ‘only’ yet another big data epidemiology finding (by Olga Basso and co-workers in a cohort of more than 50,000 women), it begs independent verification and, if confirmed, further research whether it is due to bias, biology, behaviour, or socioeconomic factors. As women tend to delay childbirth, identifying the underlying mechanism of this next-generation adverse event should become a health research priority.

Highlight January 2018

 G Coticchio M Mignini Renzini P V Novara M Lain E De Ponti D Turchi R Fadini M Dal Canto - Focused time-lapse analysis reveals novel aspects of human fertilization and suggests new parameters of embryo viability - Hum Reprod (2018) 33 (1): 23-31 DOI:


Six characters in search of an author

The title of this Editor’s Choice is taken from a play by Luigi Pirandello (a completely maddening story with an illogical storyline). Time-Lapse Microscopy (TLM) has a similar maddening history. It definitely made life in the lab more comfortable, apparently even for the embryo, and expensive TLM machines were rapidly sold. But TLM remained in search of an indication. Giovanni Coticchio and co-workers, from Monza, Italy, now decided to investigate whether application of TLM reveals new phenomena of the fertilization process that may reflect embryo quality. They showed, in a meticulous study, that combining several of the newly observed parameters (spatial dynamics of pronucleus interaction, the occurrence of the fertilization cone and of the radial cytoplasmic wave) might predict embryo quality at later stages of development. Like in Pirandello’s play however, external validation needs to be pursued before these data can help TLM (and us) any further.