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Welcome to The Visible Embryo, a comprehensive educational resource on human development from conception to birth.

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The National Institutes of Child Health and Human Development awarded Phase I and Phase II Small Business Innovative Research Grants to develop The Visible Embryo. Initally designed to evaluate the internet as a teaching tool for first year medical students, The Visible Embryo is linked to over 600 educational institutions and is viewed by more than one million visitors each month.

Today, The Visible Embryo is linked to over 600 educational institutions and is viewed by more than 1 million visitors each month. The field of early embryology has grown to include the identification of the stem cell as not only critical to organogenesis in the embryo, but equally critical to organ function and repair in the adult human. The identification and understanding of genetic malfunction, inflammatory responses, and the progression in chronic disease, begins with a grounding in primary cellular and systemic functions manifested in the study of the early embryo.

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Pregnancy Timeline by SemestersFetal liver is producing blood cellsHead may position into pelvisBrain convolutions beginFull TermWhite fat begins to be madeWhite fat begins to be madeHead may position into pelvisImmune system beginningImmune system beginningPeriod of rapid brain growthBrain convolutions beginLungs begin to produce surfactantSensory brain waves begin to activateSensory brain waves begin to activateInner Ear Bones HardenBone marrow starts making blood cellsBone marrow starts making blood cellsBrown fat surrounds lymphatic systemFetal sexual organs visibleFinger and toe prints appearFinger and toe prints appearHeartbeat can be detectedHeartbeat can be detectedBasic Brain Structure in PlaceThe Appearance of SomitesFirst Detectable Brain WavesA Four Chambered HeartBeginning Cerebral HemispheresFemale Reproductive SystemEnd of Embryonic PeriodEnd of Embryonic PeriodFirst Thin Layer of Skin AppearsThird TrimesterSecond TrimesterFirst TrimesterFertilizationDevelopmental Timeline
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Home | Pregnancy Timeline | News Alerts |News Archive Nov 28, 2013


"In countries without ART reimbursement, the Belgian policy of restricted embryo transfer can be used to achieve at least a 50% reduction in multiple pregnancy rates and associated public health costs, with no negative impact on the delivery rate per patient,
quite a relevant result to patients who have to pay ART treatments themselves."

Karen Peeraer, PhD, adjunct head of clinic, Leuven University Fertility Center,
Leuven, Belgium

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Fewer IVF embryo tranfers reduces multiple births, lowering risk, and does not have to increase costs

Research from Belgium shows that if governments restrict the numbers of embryos transferred during fertility treatment, and combine that restriction with a policy of reimbursing six cycles of assisted reproduction technology (ART), there is no detrimental impact on pregnancy and delivery rates.

However, there is a greatly reduced risk of multiple births, which have associated health risks for mother and babies and are an increased cost to the state.

A study, published online in Europe's leading reproductive medicine journal Human Reproduction, investigated delivery rates three years before and after Belgium introduced such a policy in July 2003.

It found that there was no statistically significant difference in the probability of a woman giving birth to a healthy baby (or twins) – the cumulative delivery rate (CDR) – after the legislation came in to force. The cumulative delivery rate after six ART cycles or within 36 months of starting treatment was 60.8% for women treated after July 2003 and 65.6% for women treated before.

Multiple pregnancy rates were halved as a result of the new legislation with twin delivery rates dropping from 24% to 12%.

While the effect on pregnancy and delivery rates of policies for transferring single embryos during fertility treatment have been investigated before, notably in Sweden, this Belgian study breaks new ground.

The researchers believe governments worldwide should follow a similar policy of coupling ART reimbursement with a reduction in the numbers of embryos transferred.

Dr Karen Peeraer, adjunct head of clinic at Leuven University Fertility Center, Leuven, Belgium, who led the research, said: "Our study is the first to calculate the cumulative delivery rate in a real-life scenario for up to six cycles or 36 months over a period of three years before and after the implementation of the Belgian legislation limiting the number of embryos transferred.

"This research shows that ART can maintain high delivery rates while reducing multiple pregnancy rates, the main complication of ART treatment."

Study authors write: "The results of our paper have implications for public health policies worldwide with respect to quality, safety, regulation and financial control of treatments with ART. From a public health point of view the 'Belgian model' can now be considered by other governments for application worldwide.

"In countries without ART reimbursement, the Belgian policy of restricted embryo transfer can be used to achieve at least a 50% reduction in MPR [multiple pregnancy rates] and associated public health costs, with no negative impact on the CDR per patient, quite relevant to patients who have to pay ART treatments themselves.

"The substantial amount of money saved by this policy can be used ideally to improve patient access to ART by selective reimbursement."

The researchers believe that introducing the Belgian policy may result in financial savings for governments through the reduction in multiple pregnancy rates.

"Our next step is to perform a health-economic analysis. Our aim is to show that a reduction in multiple pregnancies results in a financial benefit for the government, so that refunding six cycles of ART is still a responsible policy."

Professor Thomas D'Hooghe, last author on the paper, head of the Leuven University Fertility Center, Leuven, Belgium

Delivery rates among 463 patients treated at the Leuven University Fertility Center between 1 July 1999 and 30 June 2002 were compared with 795 patients treated at the Center between 1 July 2003 and 30 June 2006. Women younger than 43 were followed until six ART cycles had been completed, until a baby was born, until discontinuation of treatment, or for 36 months.

Before the legislation, a maximum of two or three embryos were transferred with each ART cycle.

After the legislation, laboratory costs [2] for up to six cycles of ART were funded by the state, but only if embryo transfer was restricted depending on the woman's age and the number of ART cycles she had experienced.

In patients younger than 36 years: First cycle - only one embryo can be transferred, regardless of embryo quality. Second ART cycle - one embryo transferred, but two if they are poor quality. Next four cycles - a maximum of two embryos can be transferred in each.

For patients aged between 36-39 years: Maximum of two embryos can be transferred in the first two cycles. Next four cycles - maximum of three embryos can be transferred.

For patients older than 40: No legal limit applies, but usually two or three embryos are transferred. Either fresh or frozen embryos were used in the six cycles.

The researchers looked at pessimistic, optimistic and realistic scenarios.

In the realistic scenario, they included information on the quality of the embryos in order to get a more accurate prognosis for their patients.

In the realistic scenario, researchers found that cumulative delivery rates within 36 months were comparable (65.6% versus 60.8%) between women treated before and after 2003, as well as between different age groups.

After 2003, there was a lower cumulative delivery rate within the first two cycles, but no difference within the four subsequent cycles, so that when all six cycles were taken into account there was no statistically significant difference between women treated before or after 2003.

This applied to all age groups.

Dr Peeraer adds: "We found that among women treated after July 2003 there was a higher proportion of single embryo transfer cycles, a higher singleton delivery rate and a lower twin delivery rate (12% versus 24%) compared to women treated before that date."

Prof D'Hooghe concluded: "We hope that this study, together with results from Sweden, will convince other governments to couple ART reimbursement to strict embryo transfer policies."

STUDY QUESTION What is the impact of the Belgian legislation (1 July 2003), coupling reimbursement of six assisted reproduction technology (ART) cycles per patient to restricted embryo transfer policy, on cumulative delivery rate (CDR) per patient?

SUMMARY ANSWER The introduction of Belgian legislation in ART had no negative impact on the CDR per patient based on realistic estimates within six cycles or 36 months.

WHAT IS KNOWN ALREADY The introduction of Belgian legislation limiting the number of embryos for transfer resulted in a reduction of the multiple pregnancy rate (MPR) per cycle by 50%.

STUDY DESIGN, SIZE, DURATION A retrospective cohort study with a study group after implementation of the new ART legislation (July 2003 to June 2006) and the control group, before legislation (July 1999 to June 2002).

PARTICIPANTS/MATERIALS, SETTING, METHODS CDR was compared in an academic tertiary setting between a study group after legislation (n = 795 patients, 1927 fresh and 383 frozen-thawed embryo transfer (FET) cycles) and a control group before legislation (n = 463 patients, 876 fresh and 185 FET cycles) within six cycles or 36 months, delivery or discontinuation of treatment. The CDR was estimated using life table analysis considering pessimistic, optimistic and realistic scenarios and compared after adjustment for confounding variables. In the realistic scenario we included information on embryo quality to define the prognosis of each patient discontinuing treatment.

MAIN RESULTS AND THE ROLE OF CHANCE In the realistic scenario, CDR within 36 months was comparable (all ages, P = 0.221) in study group (60.8%) and control group (65.6%), as well as in different age groups (<36 years, P = 0.242; 36–39 years, P = 0.851; 40–42 years, P = 0.840). In the realistic scenario applied to six cycles, we found lower CDRs in the study group than in the control group within the two first cycles (all ages, P = 0.009; <36 years, P = 0.007) but no difference in CDRs between the two groups within the four subsequent cycles (all ages P = 0.232; <36 years, P = 0.198). The CDR within six cycles was 60 and 65.3% for study group and control group, respectively, for all ages, and 65.8 and 70.4%, respectively, in the subgroup younger than 36 years. In women ≥36 years, CDR within six cycles was comparable in both groups (36–39 years, 43% in study versus 44.4% in control group, P = 0.730; 40–42 years, 21% in study versus 23% in control group, P = 0.786).

LIMITATIONS, REASONS FOR CAUTION A retrospective cohort study design was the only way to study the impact of legislation on CDR. Owing to the retrospective nature of this analysis over a long period of time, our data are potentially influenced by improvements in techniques and therefore improved success rates in ART over time.

WIDER IMPLICATIONS OF THE FINDINGS This ‘Belgian model’ can now be considered for application worldwide in countries with the aim to reduce the main ART side effect (high MPR) and its associated costs without a negative effect on the main intended effect (high CDR).

STUDY FUNDING/COMPETING INTEREST(S) The authors have no conflict of interest to declare. No funding was obtained for this study.

[1] "The impact of legally restricted embryo transfer and reimbursement policy on cumulative delivery rate after treatment with assisted reproduction technology", by K. Peeraer, S. Debrock, A. Laenen, P. De Loecker, C. Spiessens, D. De Neubourg, and T.M. D'Hooghe. Human Reproduction journal. doi:10.1093/humrep/det405.

[2] Before 2003 laboratory costs varied from centre to centre in Belgium but were usually between €1,000-1,500 Euros per cycle. Medication costs are partially reimbursed by the state and patients still need to pay around €100 per cycle. Costs of blood tests and ultrasound monitoring are also partially reimbursed by the state and patients still need to pay approximately €100 per cycle. The policy on reimbursement (and costs) for medication, blood tests and ultrasounds is largely unchanged from before 2003.