POPI-Plus calculator predicts chance of live birth after positive beta-hCG

Researchers in a 2023 study developed a model to predict the chance of live birth after a positive β-hCG (beta-hCG), using the first measurement and a second one taken 48 hours later.

This study wanted to develop a calculator for predicting live birth after a pregnancy by IVF. They found that 4 factors were strongly linked to this: the first and second β-hCG, female age at time of retrieval and the treatment type.

This study can help patients predict their chance of live birth after a positive β-hCG, with high (but not perfect) accuracy.

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Study details

This section covers key details of how the study was performed, including the number of patients and their characteristics, how they were treated, and other methods used. For those who aren’t interested in these details, and just want to see the results, you can go ahead and skip this part.

• This study took place at two IVF centers in Canada between 2012 and 2016.
• Patients had a single untested embryo transferred and became pregnant. Patients without a positive pregnancy were excluded.
• The first β-hCG was taken 13 days after a day 2 embryo transfer, 12 days after a day 3 transfer and 10 days after a day 5 (blastocyst) transfer. The second β-hCG was taken 48 hours after the first one.
• An ultrasound evaluated clinical pregnancy 3 weeks after the second β-hCG.

In terms of sample size, there were 1,995 pregnant patients included, with 70% being used to train the POPI-Plus model and 30% used to validate it.

In terms of baseline characteristics, the average age was about 33, with most transfers being day 5 blastocysts, followed by day 3, day 2 and day 6 (~46%, ~38%, ~13%, ~1%). Most transfers were fresh, followed by frozen medicated cycles and modified natural cycles.

Development of the POPI-Plus calculator

Using a statistical method, the researchers identified 4 factors that predicted live birth after IVF:

• The patient’s age at egg retrieval.
• The first β-hCG.
• The second β-hCG.
• The IVF treatment type.

They found that a faster rising β-hCG was associated with increased odds of a live birth.

The accuracy of the model was tested on 597 patients:

• POPI predicted correctly: 412 patients had a live birth, and 63 patients didn’t have a live birth.
• POPI predicted incorrectly: 102 patients had a live birth, and 20 patients didn’t have a live birth.

Their model had an AUC of 0.76 during training and 0.78 during validation, with an overall accuracy of 79.56%.

The POPI-Plus calculator and how to use it

Note that this calculator applies only to patients who have transferred a single blastocyst or cleavage stage embryo, either fresh or frozen (medicated FET or a modified natural FET).

To use the calculator, you need to enter your first β-hCG from exactly 10 days after a blastocyst transfer or 12 days after a day 3 transfer (= 15 days after the egg retrieval). The second β-hCG has to be measured exactly 2 days later.

It will also ask you your age at the time of egg retrieval and the treatment type. The treatment type can be:

• Stimulated IVF (fresh transfer)
• Natural IVF (modified natural)
• Frozen embryo transfer (medicated FET)

It will then give you the chance of a live birth! The calculator can be found here.

Conclusions

The POPI-Plus calculator offers a personalized way to predict the chance of live birth after transfer, and is the first to consider how β-hCG rises by including the second β-hCG measurement.

The model was built using specific criteria, so this needs to be considered (ie. the first β-hCG has to be measured from exactly 10 days after a blastocyst transfer).

The authors point out that the model predicts a reduced chance of live birth when using a modified natural or medicated FET, compared to a fresh transfer. However, a recent RCT found no difference between fresh and frozen cycles (reviewed here), although other studies have contradicted this.

Limitations of this study include that they didn’t include BMI, endometrial thickness, progesterone administration method and ethnicity.

Reference

Mourad A, Antaki R, Rowen M, Levesque E, Lapensée L. The POPI-Plus tool: Prediction model of outcome of pregnancy in IVF from a large retrospective cohort. Fertil Steril. 2023 Dec 1:S0015-0282(23)02031-9. doi: 10.1016/j.fertnstert.2023.11.035. Epub ahead of print. PMID: 38043845.

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About Embryoman

Embryoman (Sean Lauber) is a former embryologist and the founder of Remembryo, an IVF research and fertility education website. After working in an IVF lab in the US, he returned to Canada and now focuses on making fertility research more accessible. He holds a Master’s in Immunology and launched Remembryo in 2018 to help patients and professionals make sense of IVF research. Sean shares weekly study updates on Facebook, Instagram, and Reddit regularly. He also answers questions on Reddit or in his private Facebook group.

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