Abstract
The 27th Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE) for the year 2011 was held in Stockholm (Sweden) between the 3rd and 6th of July. The ESHRE conference is always a great annual opportunity to connect with friends in the profession from across the world was well attended by 8361 participants. The ESHRE has grown from strength to strength since its first annual meeting in Bonn in 1985 and the meeting is now one of the most important meetings on fertility and embryology. The meetings are attended by professionals from all over the globe with very good attendance from Asia as well. As the scale of the meeting is very large, a summary to present some of the highlights is a useful tool and this article aims to do that.
The 27th Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE) was held in Stockholm (Sweden) on 3–6 July 2011. For myself, this year was particularly special as my paper on comparing the acute energy metabolism of granulosa cells between metformin-pretreated and untreated women with polycystic ovary syndrome undergoing assisted conception was selected for an oral presentation. Attending the inauguration ceremony on the day of arrival and meeting Professor Allan Trounson in person was a particular highlight; a part of my doctoral research was on oocyte metabolism and in vitro maturation, and Professor Trounson is one of the pioneers of in vitro maturation. An additional attraction was the cultural program, which is always a treat to the delegates.
The first keynote lecture on the first day of the conference was on ‘Aneuploidy in humans: what we know and what we wish we knew’ by Terry Hassold (Centre for Reproductive Biology, WA, USA). It was well attended. The key message was that there are multiple routes to aneuploidy, which include the known and unknown aberrations. Maternal age and genetic recombination are the two main reasons for nondisjunction leading to aneuploidy in the embryos. Why female gametes are more prone for nondisjunction during meiosis has not been very clearly understood. It could be the ‘selection process’ for the fittest to survive. While the risk for trisomy 16 increases from the age of 20 years, that of trisomy 21 and 18 increases exponentially after the age of 35 years. The second keynote lecture was on the outcome of intracytoplasmic sperm injection using fresh versus vitrified mature oocyte. The speaker LF Rienzi (Genera Centres for Reproductive Medicine, Rome, Italy) highlighted oocyte vitrification as the most important fertility option in Italy where surplus embryo cryopreservation is not possible due to strict legislation. As women want more economic independence and high standards of education before starting a family, oocyte vitrification is very relevant to them. The lecture listed the factors that influence the embryo development of vitrified oocytes following intracytoplasmic sperm injection. The selection of cryopreservation methodology was mentioned as one such important factor.
Endometriosis affects approximately 100 million women in the prime of their lives, and severely affects their quality of life. The session on endometriosis and surgery on 4 July 2011 included presentations on the dilemma of excision of endometriomas, and the risk of reduced ovarian reserve following excision. Laparoscopic suturing of the ovary after ovarian cystectomy of endometrioma was shown to be superior to bipolar coagulation in terms of preserving the ovarian reserve by minimizing the thermal damage to healthy follicles. In the meta-analysis ‘The impact of fibroids and fibroid management on reproductive success’ presented by W Catherino (Uniformed Services University, MD, USA), the speaker suggested that the outcome of IVF could be compromised in the presence of fibroids.
Those interested in oocyte and embryo metabolism were attracted to the presentation on ‘Glucose consumption by day 4 and 5 embryos is predictive of pregnancy and sex of the embryo’. Female and male embryos were shown to differ in their energy metabolism, such that the glucose consumption by female embryos was 15% higher than their male counterparts by day 5 of embryo development. Similarly, embryos that resulted in a pregnancy consumed more glucose than those that did not result in a pregnancy.
A particularly interesting session of the day was the debate on ‘Whether obese women should not receive treatment until they have lost weight’. M Hamilton (University of Aberdeen, Aberdeen, UK) presented a clinician’s viewpoint, highlighting the negative implications of obesity on fertility and the risks of obesity on a pregnancy. W Dundrop (University of Maastricht, Maastricht, The Netherlands) presented the ethical side of the problem. To our surprise, the expectation to hear a unanimous “no” to fertility treatment until obese women lost weight was thwarted, and several clinicians around the world expressed their sympathy towards these women, stressing the importance of supporting weight loss in order to motivate them. The participants concluded that women should be made aware of the implications of obesity and encouraged to achieve a target weight before fertility treatment.
Another highlight of the day was the presentation in the basic research session, which was well attended. The research has shown that acute glucose consumption and pyruvate production by granulosa cells is decreased, while lactate production is increased in women with polycystic ovary syndrome compared with normal controls. Metformin pretreatment during intracytoplasmic sperm injection improved the metabolic profile of granulosa cells bringing it closer to that of controls. The parallel session on ethics and law was also well received. The work presented from Newcastle reiterated the fact that removal of donor anonymity in the UK has significantly reduced the number of egg and sperm donors in the country. Nevertheless, the number of donor drop-outs after initial screening has also significantly decreased, indicating the commitment of the altruistic donors. The egg-sharing scheme practiced in Newcastle (UK) informed the audience that couples donate theirs eggs not only for treatment of others, but also for research.
Tests for ovarian reserve, customized ovarian stimulation protocols and markers of oocyte and embryo quality form the hallmark of a successful IVF cycle. The Merk–Serono symposium later that day dealt with these vital topics. Conclusive proof that the response of the antral follicle to follicle-stimulating hormone (FSH) is a measure of its health is lacking, although it has been widely suggested by various authors. Renato Fanchin (Hospital Antoine Béclère, University Paris, Paris, France) put forward the follicle output rate (FORT) as an innovative index of assessment of oocyte health. FORT is assessed by the ratio between the number of preovulatory follicles obtained in response to FSH administration and the preexisting pool of small antral follicles, and has been found to correlate positively with the outcome of IVF embryo transfer. FORT shows promise as an objective approach to assessment of the actual response of follicles to exogenous FSH, not influenced by the size of the preexisting cohort of antral follicles.
On the second day of the conference, a large audience was seen at the lecture ‘Mitochondrial metabolism and embryo development’ by M Wilding (Villa Del Sole, Napoli, Italy). The lecture presented evidence to support the idea that mitochondrial metabolism of the oocyte has an important role in determining embryo development. In the absence of optimal aerobic respiration in the mitochondria, embryos may continue to cleave, develop and implant but may not produce a live offspring. Advanced maternal age reduces the mitochondrial activity predisposing the oocyte/embryo for anaerobic respiration, resulting in chaotic mosaicism and poor pregnancy outcome.
Selection of healthy gametes and healthy embryos for transfer remain crucial elements of IVF treatment. Peter Humaidan (The Fertility Clinic, Viborg Hospital, Viborg, Denmark) presented a comprehensive overview of the methods tried so far, such as spindle and zona pellucida imaging, metabolonomics of embryos and study of embryo kinetics. Thus far, time-lapse imaging appears to be the best available method for picking up the healthiest embryos with maximum potential for implantation. Humaidan also emphasized the point that the application of the biomarkers of ovarian response, such as age, antral follicle count, anti-Müllerian hormone (AMH) and FSH, is important in formulating individualized controlled ovarian stimulation (iCOS) for optimizing outcome in IVF.
In order to enrich our knowledge on the predictors of oocyte quality during IVF, we joined the session on ‘Deep insight into oocyte quality’. The ultimate marker of oocyte quality is live birth rate per oocyte, and the available literature reports a live birth rate of 4.7 per oocyte in natural cycles of donors. Currently, female age is the most reliable indicator of oocyte quality. There are scientific reports supporting the notion that culture conditions and additives to culture media such as hormones and nutritional factors may influence oocyte quality. T Ebner (Landes- Frauen- und Kinderklinik, Linz, Austria) also explored the possible correlation between AMH and oocyte quality. Ebner concluded that very low AMH levels correlated well with oocyte morphology in terms of dark ooplasm.
An entire session was devoted to ovarian stimulation, which continues to present challenges to the clinician. A low serum progesterone level (<0.45 ng/ml) has been shown to contribute to poor outcome in IVF, and E Bosch and colleagues (Instituto Valenciano de Infertilidad, Universidad de Valencia, Valencia, Spain) suggested that the addition of luteinizing hormone (LH) to these patients improves outcome. L Thuesen (Copenhagen University Hospital Rigshospitalet, København, Denmark) and coworkers demonstrated that supplementation of human chorionic gonadotropin from the first day of stimulation is linked to better quality embryos and pregnancy rates. AM Abou-Setta’s (Alberta University, Canada) group presented a systematic review of 30 randomized, controlled trials on whether the addition of LH activity to FSH provides an advantage in stimulation protocols in IVF, and concluded that the addition of LH did not confer a significant benefit.
The free-communication session on agonists and antagonists was very lively. Many delegates were disappointed when they were turned away due to lack of space in the large hall, which overflowed. One paper compared the outcome of commencing FSH stimulation on day 2 versus day 5 in an antagonist cycle. The results showed an increase in the development of high-grade embryos using day 2 stimulation compared with day 5 stimulation (31 vs 25%). Although some clinicians commence stimulation on day 5 to try and reduce the total number of follicles, and hence, the risk of ovarian hyperstimulation syndrome, the paper concluded that day 5 stimulation was associated with poor embryo development. The paper comparing the effectiveness of ‘mini-dose’ gonadotropin-releasing hormone agonist and gonadotropin-releasing hormone antagonist in poor responders was challenged by a significant number of delegates. The results favored the use of triprolide 0.05 mg daily from the mid-luteal phase in a long agonist protocol, resulting in higher clinical pregnancy rate compared with the short antagonist protocol (21 vs 16%). However, the criticism was that the dose used by the researchers was not actually a ‘mini-dose’, and therefore the validity of the results was questioned. I Cedrin-Durnerin (Reproduction Hôpital Jean Verdier, Bondy, France) received a particularly warm welcome for her presentation. Cedrin-Durnerin’s research concluded that pretreating women with a few days of estrogen in an antagonist protocol facilitated planning egg collections during weekdays in large IVF centers without compromising the pregnancy outcome. Cedrin-Durnerin showed that using micronized estrogen (4 mg) is better than using the combined contraceptive pill for this purpose. Although the author suggested a washout period of 24 h after estrogen use before commencing FSH stimulation, some of the learned delegates in the audience commented that such washout is unnecessary when estrogen alone is used. A short course of estrogen alone does not suppress endogenous FSH, while the use of the combined oral contraceptive pill does and therefore needs a minimum washout period of 5 days before commencing FSH stimulation.
The symposium organized by Ferring Pharmaceuticals Ltd (West Drayton, UK) attracted a large audience. The session commenced with the presentation of their new data from the trial ‘Megaset’ comparing the effectiveness of highly purified human menopausal gonadotropin and recombinant FSH in antagonist cycles. The results confirmed noninferiority of highly purified human menopausal gonadotropin in terms of blastocyst development. The incidence of ovarian hyperstimulation syndrome was similar in both groups.
Opinion has always been divided on the role of luteal-phase support in the outcome of IVF and pregnancy. Another company symposium organized by IBSA Pharma (Pambio-Noranco, Switzerland) revisited this controversy and generated much debate. AR Genazzani (University of Pisa, Pisa, Italy) presented an overview of the immunomodulatory role of progesterone in early pregnancy. Progesterone suppresses the natural killer cell activity, masks fetal antigens from the maternal immune system and synthesizes progesterone-induced blocking factor in order to facilitate early embryo implantation. C de Geyter (University Hospital, Basel, Switzerland) presented the data from a large multicenter, randomized, controlled trial conducted in 13 European centers comparing the effectiveness of a new means of delivery of progesterone in the form of subcutaneous progesterone with vaginal progesterone gel. The subcutaneous progesterone was found to be as effective as vaginal progesterone.
The free communication session on PCOS updated the audience on various aspects of the condition. Although the occurrence of insulin resistance was reported to be similar between the generations, the occurrence of diabetes was higher in the second-generation women. The endometrial development was reported to be slow in women with PCOS compared with controls, possibly due to altered protein expression. There was also a recap on various treatment strategies in women with PCOS, which emphasized weight loss as the first-line treatment in overweight subjects.
The welfare of the children born from assisted conception treatments has always been a vital session in ESHRE meetings. The Danish and French reports showed that singletons born from frozen embryo transfer cycles were ‘large for dates’ (>4.5 kg). The observations reminded the audience of large offspring syndrome, which has been described in animals. Although in animals large offspring syndrome is associated with congenital malformations, a similar association has not been identified in humans. The question was whether, such large for dates embryos, in frozen cycles could result from culture-related factors such as the use of serum in the culture medium. More research is needed to address this question.
The area dedicated for poster display had a busy turnover of participants throughout the conference. The posters covered a wide spectrum of reproductive medicine, including reproductive imaging, endocrinology, pathology, basic science, embryology, fibroid uterus, genetics, menopause and assisted reproductive technology.
One of the key events in ESHRE 2011 the pre-congress workshops, which focused on subjects such as embryology, the oocyte, reproductive endocrinology, endometrium, andrology, fertility preservation, safety and quality in assisted reproductive technology and reproductive surgery. Special interest groups headed by a coordinator brought together experts in the field and information on the latest developments and updates, while also steering further scientific search in that field. These workshops are valuable sessions both for established practitioners and trainees.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.