Previous highlights 2013

Highlights December 2013

Birthweight and placental weight; do changes in culture media used for IVF matter? Hum. Reprod. (2013) 28 (12): 3207-3214. doi: 10.1093/humrep/det376 by Anne Eskild et al. Human Reproduction was the first to draw attention to a fascinating but also disturbing effect of IVF: having been, as an embryo, for only 2-3 days in either of two culture media was associated with a difference in birth weight of 245 grams. Subsequent studies were unable to replicate this. But now Anne Eskild and co-workers from Tom Tanbo’s group in Oslo, Norway, in a retrospective observational study with historical controls, have confirmed the original findings. In their study, in IVF singletons, the mean birthweight was 3352 grams with Medicult ISM1, 3441 grams with Vitrolife G-1 PLUS, and 3448 grams with Medicult Universal (P < 0.05). The corresponding mean placental weights were, 693, 704 and 684 grams (P < 0.05). Of course, the differences are minimal and statistical significance was reached because of the large numbers (400-1500 IVF births per culture medium group), but the message is clear and loud, especially when considering the Barker hypothesis: a few days in a certain environment as an embryo may make a difference in later life. To be continued.

Highlights November 2013

Twenty years of Cochrane reviews in menstrual disorders and subfertility Human Reproduction 2013, 28: 2883-2892. doi: 10.1093/humrep/det334 Cindy Farquhar et al., on behalf of the Cochrane Editorial Board of the Menstrual Disorders and Subfertility Groups

When the Scottish physician and epidemiologist Archibald Leman Cochrane died in 1988 the Cochrane Collaboration did not yet exist. At this moment, 25 years later, there are 54 Cochrane Review Groups, seven of which are involved in women’s health, in the broadest sense of the word. Archie Cochrane pioneered evidence based medicine ‘avant la lettre’. In this issue of Human Reproduction ten of his most eminent followers shed their light on the significance of the Cochrane Menstrual Disorders and Subfertility Group (CMDSG) for the understanding of clinical research in our field, and on its application to reproductive health care. The CMDSG, with 25 editors based in eight countries, has published 170 full Cochrane reviews, and this article presents an overview of them. The paper ends with a view to the future, The Cochrane Collaboration will adopt the Green Open Access model that also the Human Reproduction journals employ: all articles will become freely available after 12 months, or immediately upon publication (Gold Open Access), at a cost to authors and/or funders.

Highlights October 2013

Phthalates may promote female puberty by increasing kisspeptin activity Hum. Reprod. (2013) 28 (10): 2765-2773. doi: 10.1093/humrep/det325. CY Chen and co-workers:

Kisspeptin is a fascinating, appropriately named molecule with an important role in reproductive function, a role that is gradually becoming elucidated. CY Chen and colleagues from Taiwan now report on the correlation between phthalate levels, kisspeptin and the occurrence of precocious puberty in girls. The finding is the more important since we all have several types of phthalates circulating in our body. Phthalates are used to increase the flexibility of plastics, and as such can be found in toys, tools and household appliances. They also occur in waxes, printing ink, pharmaceuticals and, especially, food products. They are released as plastics break down in the environment. Diet appears to be the main source of phthalate accumulation in our bodies. These same substances now appear to enhance the role of kisspeptin in puberty. Kisspeptin neurones in animals have been shown to express oestrogen receptors. Whereas the food authorities are step by step banning phthalates, I predict that this will not be the last time that we will learn about their disturbing role in reproduction.

Highlights September 2013

Emergency IVF for embryo freezing to preserve female fertility: a French multicentre cohort study. Human Reproduction 2013;28:2381-2388. B Courbière and co-workers:

Blandine Courbière and co-workers from Marseille report on a French 14 centres study on emergency IVF in patients destined to undergo gonadotoxic treatment, predominantly for malignancies. Together 56 cycles were started in 52 patients. An average number of 4.2 embryos could be frozen per cycle. In 34% of patients gonadotoxic treatment was delayed because of the request for fertility preservation. Three patients died as a consequence of their disease. Eleven of the remaining 49 (22%) requested thawing and transfer of (some of) their frozen embryos. In ten a transfer was performed. One biochemical pregnancy occurred and one miscarriage. Three pregnancies proceeded to the delivery of a liveborn baby. This constitutes 27% of the couples applying for embryo transfer. Although embryo freezing has been established as a successful and safe option in subfertility patients with spare embryos, this study is one of the first to offer an insight in the long term outcome of emergency embryo freezing for cancer patients. The outcome is reassuring and emphasizes the importance of counselling young cancer patients for this possibility.

Highlights August 2013

Reproductive prognosis in daughters of women with and without endometriosis. Human Reproduction (2013) 28 (8) 2284-2288. T. Dalsgaard, M.V. Hjordt Hansen, D. Hartwell and Ø. Lidegaard

Tórur Dalsgaard and co-workers from Copenhagen, Denmark showed that daughters of women with endometriosis have over a two-fold higher risk of endometriosis but no decreased long-term reproductive prognosis compared to controls. They compared 24,691 women diagnosed with endometriosis during the period 1977-1982 to 98,764 age-matched women without a diagnosis of endometriosis, and studied whether their daughters had endometriosis diagnosed and what their long-term reproductive performance was. The findings confirm an increased occurrence of endometriosis in some families, but do not back up the presumed association between endometriosis and subfertility. The most important limitation of the study, as stated by the authors themselves, was the lack of data concerning the women’s aspiration to become pregnant and the fact that some (many?) women with endometriosis might never be diagnosed with the condition.  

Highlights July 2013

Reproductive and obstetric outcomes after radical abdominal trachelectomy for early-stage cervical cancer in a series of 31 pregnancies. Human Reproduction 2013;28:1793-1799H. Nishio and co-workers.

This is a large series of 114 patients with early-stage cervical cancer from Tokyo, Japan. Hiroshi Nishio and colleagues report the follow-up of these patients after having been treated by means of radical abdominal trachelectomy (surgical removal of the uterine cervix, with preservation of the uterine body). Three things are important here: safety (cancer survival), postoperative fertility (pregnancy rate), and obstetric outcome (liveborn rate). Sixty-nine patients pursued a pregnancy during the follow-up period, of whom 25 conceived at least once (36%). Seven conceived spontaneously, 1 after IUI, and 17 after IVF. Obstetrical complications included first and second trimester miscarriages, preterm births and a high caesarean section rate. We will have to wait for the long term follow-up to learn more about the safety of the procedure. So far this study fits the developing picture that shows cancer is curable in many women nowadays, or at least that in a selected group of women developing a malignancy does not always have to mean that couples should abandon their child wish.

Highlights June 2013

Consensus on current management of endometriosis, Hum. Reprod. 2013;28:1552-1568. Neil P Johnson and Lone Hummelshoj, for The World Endometriosis Society Montpellier Consortium

The World Endometriosis Society (WES) convened a meeting in September 2011 in Montpellier in which 56 representatives of 36 national and international medical and non-medical societies and patient organizations were engaged in intense dialogue to reach a global consensus on the management of endometriosis. This unique meeting was the culmination of many months of arduous efforts by dedicated clinicians and scientists, and laborious electronic exchanges of ideas. Linda Giudice, the vice-chair of the WES commented: “The dedication of the attendees and the organizers to having conclusions based firmly on scientific evidence and acknowledging areas where there is lack of evidence is a credit to the rigor with which this endeavor was undertaken with the long-term goal of improving the wellbeing of millions of women and teens afflicted with this disease worldwide”. Evidence based medicine is the skill – perhaps even the art – of being able to integrate the best available scientific evidence and to apply it to each patient’s individual situation. Or, as WES president Paolo Vercellini put it, “it is more than ‘recommendations’ or ‘a guideline’; it is a concentrate of immense clinical experience, research efforts, and cooperation with endometriosis patients”. This is a exceptional document indeed. As an Editor-in-Chief of Human Reproduction I am proud that the authors have picked our journal to publish it.

Highlights May 2013

Inter-clinic variation in the chances of natural conception of subfertile couples,Hum. Reprod. 2013;28:1391-1397. R.I. Tjon-Kon-Fat et al. If you would send 2916 subfertility couples to 21 different clinics, what would be their chances of natural conception within one year? About 30%, right? Right! Would you expect differences between clinics? No. Wrong! Tjon-Kon-Fat and co-workers did exactly that: they performed a prospective cohort study in 21 clinics that treated more than 20 couples per year and found significant differences. The natural conception rates ranged from as low as 8% to as high as 44% per year per clinic (!), and the differences could neither be explained by differences in characteristics of the patients nor the clinics. The authors conclude: “We found significant inter-clinic differences in natural conception chances for subfertile couples, which remain after adjustment for well-recognized predictors and type of clinic and accounting for sampling variation. These findings may seem counterintuitive, as these couples did not receive active treatment and as such we did not expect differences in outcome between these clinics”. “May seem counterintuitive” is a mild way of putting it. I would say astonishing. 

Highlights April 2013

Seminal and Molecular Evidence that Sauna Exposure Affects Human Spermatogenesis, Hum Reprod 2013;28: 877-885. Andrea Garolla et al Just when you thought sauna was safe, here comes a study – unfortunately not randomised – from Italy suggesting the opposite. Andrea Garolla and co-workers from Padova put 10 healthy Italian men in a sauna for three months (intermittently) and compared their semen before and after this typically Finnish heat challenge. Sperm count and motility decreased. Decreases in the percentage of sperm with normal histone-protamine substitution, chromatin condensation and mitochondrial function were noted as well, and a strong simultaneous up-regulation was seen of genes involved in response to heat stress and hypoxia. The good news, however, for our new Chairman Elect is that all these depressing effects were completely undone six months after the last sauna exposure. We will wait for the reply from the North.

Highlights March 2013

Accumulation of numerical and structural chromosome imbalances in spermatozoa from reciprocal translocation carriers, Hum Reprod 2013; 28: 840-845 by A. Godo, J. Blanco, F. Vidal and E. Anton

Godo and co-workers, from Barcelona, Spain, performed a FISH study on spermatozoa of eight reciprocal translocation carriers and found that the selected population of aneuploid and diploid spermatozoa showed significantly increased frequencies of unbalanced segregation modes of the rearranged chromosomes. Although traditional FISH was used and therefore only five chromosomes could be analyzed, their findings suggest a gathering of chromosomal abnormalities in a given nucleus. The findings shed new light on the meiotic mechanisms involved in non-disjunction occurring in gametes from reciprocal translocation carriers.

Highlights February 2013

Elective single embryo transfer in women aged 40 to 44 years, Hum reprod 2013; 28: 331-335 by Niinimäki M, Suikkari AM, Mäkinen S, et al.

There is an astonishing culture clash to be found in the pages of this month’s Human Reproduction. Maarit Niinimäki and colleagues from Finland, the country that brought us eSET, report on a (retrospective) series of 628 women between 40 and 44 years of age receiving electively either one or two embryos in fresh and subsequent frozen cycles and achieving live birth rates of 22.7 and 13.2% per transfer respectively, with low twin rates of 6.7 and 8.3%. The authors, from Oulu and Helsinki, conclude that for older women having a good prognosis, an eSET policy can be applied with acceptable cumulative clinical pregnancy rates and live birth rates.

From the other side of the Great Divide, Norbert Gleicher, from New York, USA, comments (Hum Reprod 2013;28:294-297) that he couldn’t disagree more: “Is it really ethically acceptable to urge 40- to 44-year-old women to reduce their immediate pregnancy chances? Is it ethically acceptable to do this to even younger women? (…) No patient can ever be guaranteed that she will be given a second chance to conceive, once she decides to split the initial 2ET chance into two consecutive eSET cycles”. He concludes that the time has come to reconsider eSET policies, not only for older women, but for all women who have to rely on IVF to start a family.

Highlights January 2013

Neonatal outcome and congenital malformations in children born after ICSI with testicular or epididymal sperm: a controlled national cohort study, by J Fedder, A Loft, ET Parner , S Rasmussen, A Pinborg from Horsens Hospital, in Denmark.

We owe it to the excellent Scandinavian registries that clinical problems that cannot be addressed experimentally can still be solved. This study from Denmark studied neonatal outcome and congenital malformations in 466 children born after epididymal or testicular sperm aspiration and compared them to 8967 ICSI children, 17,592 IVF children, and 63,854 children born after natural conception. The reassuring finding is that using surgically retrieved sperm is equally safe as conventional IVF and ICSI and that neonatal outcome does not differ from that after natural conception.