Abstract More than four decades have passed since the birth of the first infant conceived through the use of assisted reproductive technology (ART). During this time, ART has increased the chance for millions of people who have trouble conceiving to achieve a healthy pregnancy and birth. In the early years of IVF/ICSI, clinicians may have transferred all available embryos into the uterus because of the low overall treatment success at the time. However, with medical and technical improvements in ART, the transfer of multiple embryos led to a greater number of multiple pregnancies, compared to spontaneous pregnancies. Multiple pregnancies are associated with a wide range of maternal and neonatal complications. This is why at present, the transfer of one embryo is considered the preferable route towards the key objective of ART and at present this is recommended by several international and national professional organisations such as ESHRE and ASRM. However, these recommendations are not followed in many countries, as can be observed in annual reviews. Double embryo transfer (DET) remains a viable alternative to elective single embryo transfer (eSET) in many clinics. The aim of the presentation is to highlight the place of double embryo transfer in the current practice of ART while taking into account best evidence from clinical studies. The presentation will present results from ESHRE’s guideline on the number of embryos to transfer in IVF/ICSI as well as some results from the surveys of the guideline development group (GDG), the most important of which is the survey to European infertility patients performed together with Fertility Europe, Europe’s patient organisation.

To compare cumulative term live birth rates (ctLBR) after elective single embryo transfer (eSET), using data from two countries -- Finland where cleavage stage (day 2/3) eSET is almost exclusively used, and the U.S. where blastocyst (day 5/6) eSET is more common. Retrospective cohort study comparing data from Finland’s largest infertility clinics (LUMI database, cleavage stage eSET performed in 50.5% of all fresh cycles) with data from the U.S. National Assisted Reproductive Technology (ART) Surveillance System (blastocyst eSET performed in 3.9% of all fresh cycles). The analysis included all fresh, non-donor eSET (n=16,276) and subsequent frozen embryo transfer cycles (n=11,625) performed during 2008-2012 in the U.S. and Finland among women aged ≤40 years with no prior use of ART. U.S. clinics were classified into those with high (≥52 cases/year) and low (<52 cases/year) use of eSET. We used multivariable logistic regression to evaluate the association between ctLBR and embryo stage, after controlling for patient and treatment characteristics. In Finland 2,046 cleavage stage eSETs were performed; in the U.S. 7,202 and 5,272 blastocyst eSETs were performed in clinics with low and high eSET use, respectively. The ctLBR was lower in cleavage stage Finnish cycles (42.7%) than in U.S. blastocyst cycles (low eSET use: 57.5%, high eSET use: 60.3%, P=0.0003). Compared with cleavage stage Finnish cycles, U.S. blastocyst cycles were associated with higher odds of term live birth (low eSET use: OR 1.60, 95% CI 1.41-1.81; high eSET use: OR 1.91, 95% CI 1.68-2.16). Gonadotropin dose per oocyte was higher in cleavage stage Finnish cycles (184.3±141.0 IU), compared with U.S. blastocyst cycles (low eSET use: 154.2±129.5, P<0.0001; high eSET use: 158.1±223.8, P<0.0001). The estimated number of cleavage stage transferrable embryos was higher in the U.S. blastocyst cycles (low eSET use: 9.6 ± 5.5; high eSET use: 8.8 ± 5.4) than in cleavage stage Finnish cycles (5.8 ± 3.3, P<0.0001). Single blastocyst transfer in the U.S. is associated with higher ctLBR than cleavage stage embryo transfer in Finland. Probable reasons for these findings are high selectivity of patients for blastocyst eSET in the U.S. which constitute only 3.7% of all fresh cycles. These women have better ovarian response, as indicated by lower use of gonadotropins during stimulation and more embryos available for transfer, compared to Finnish cleavage stage patients, who are selected for eSET on a much wider basis.

The use of embryo freezing is continuously increasing. However, little is known about the reproductive potential of the top quality frozen-thawed embryos as compared to top quality fresh embryos. Retrospective study. 4686 consecutive fresh IVF/ICSI with embryo transfer and 3659 frozen-thaw (FET) embryo transfer cycles performed in the years 1998-2007. FET cycles were linked with their respective fresh stimulation ones. Fresh and frozen-thawed embryos were graded using the same criteria. Top quality embryos were transferred in 2653 fresh and 543 FET cycles. Of these, we evaluated elective single embryo transfer (eSET, 1217 fresh cycles) and single embryo transfers in FET (225 FET cycles) with top quality embryos. Clinical pregnancy rate (PR) was the primary outcome variable. On average, FET patients were older than the fresh cycle ones (32.0 ± 4.0 vs. 31.1 ± 4.4 years, P=0.004). However, the age at freezing was similar to the age in the fresh cycles (30.8 ± 4.0 years, P=0.3). BMI, main infertility diagnosis and the percentage of ICSI were also similar between the groups. In fact, in 66.2% (149/225) of the FET cycles, a fresh cycle eSET had taken place. PR was similar in the fresh and FET groups (392/1217, 32.2% vs. 49/225, 30.7%, P=0.7). Live birth rate tended to be lower in the FET patients (286/1217, 23.5% vs. 44/225, 19.6%, P=0.2). The number of multiples was low in the both groups (2/392 vs. 0/69, P=1.0). The study shows that more than half of top quality frozen-thawed embryos originate in an eSET cycle, underlining the role of eSET. Embryos which retain top quality characteristics after freezing, thawing and subsequent culture have a similar pregnancy potential as fresh top quality embryos. However, live birth rate after the transfer of a single top quality embryo in FET might be slightly lower possibly due to subtle embryo damage during freezing and thawing.

Obesity is associated with an increased risk of miscarriage both in spontaneously conceived pregnancies and after fertility treatment. The aim of the present study was to compare the effect of obesity on pregnancy outcome in fresh IVF/ICSI, in spontaneous and hormonally substituted FET cycles. Retrospective study. Analysis was carried out on 4057 consecutive pregnancy cycles performed during the years 1999–2004 in five Finnish infertility centers. Two groups were studied: obese, with BMI ≥ 27 kg/m2 (n = 552, 13.6%) and non-obese, with BMI < 27 kg/m2 (n = 3505, 86.4%). Treatment types (fresh cycles, spontaneous and hormonally substituted FET) were studied independently. Univariate logistic regression was used to assess the independent effect on miscarriage of obesity, age, diagnosis, secondary infertility, positive history of previous miscarriage, origin of the embryo (IVF vs. ICSI), number of embryos transferred and transfer of at least one top quality embryo. We also studied the effect of stimulation protocol (GnRH agonist vs. GnRH antagonist) and elective single embryo transfer in the fresh cycles, as well as the use of luteal phase progesterone (in spontaneous FET only) and the use of GnRH agonist (in hormonally substituted FET only). Multivariate logistic regression was performed with the variables showing independent effect in the univariate analysis. Miscarriage rate (MR) was similar in obese and non-obese women in the fresh (62/332, 18.7% vs. 309/2121, 14.6%, P=0.06) and spontaneous FET cycles (13/90, 14.4% vs. 118/846, 13.9%, P=0.9). However, in hormonally substituted FET cycles, obese subjects had a higher MR than non-obese ones (54/130, 41.5% vs. 117/538, 21.7%, P<0.0001). Irrespective of BMI, women who received hormonal substitution had higher MR than women in the corresponding group of spontaneous FET cycles (P<0.0001). Multivariate logistic regression revealed that obesity was an independent risk factor for miscarriage in hormonally substituted FET only (odds ratio 2.6, 95% confidence interval 1.6–4.3). Age and the history of previous miscarriage were the other factors with significant effect on MR in fresh and FET cycles. Obesity increases MR in hormonally substituted FET cycles but not in fresh IVF/ICSI cycles or FET after spontaneous ovulation. In addition, hormonal substitution in FET is associated with a higher MR in all women.