Intrauterine hCG Infusion Before Embryo Transfer in IVF: From Initial Hope to New Evidence Reappraisal

The success of Assisted Reproductive Technology (ART) depends not only on embryo quality but also on the complex interaction between the embryo and the endometrium, which plays a decisive role in implantation and pregnancy continuation. Despite significant advances in embryo selection, blastocyst culture, embryo freezing, and genetic techniques, a considerable portion of IVF cycles still fail due to implantation failure or the inability to achieve a successful pregnancy.

This issue has led to the introduction of various auxiliary treatments or "IVF add-ons" in recent years, aimed at improving endometrial receptivity. One of these methods is the intrauterine infusion of human chorionic gonadotropin (hCG) before embryo transfer.

The core idea behind this method is based on the natural role of hCG in the early stages of pregnancy. Prior to implantation, the embryo begins to secrete hCG, which can influence molecular processes associated with endometrial receptivity, immune system regulation, and preparing the uterine environment via LH/hCG receptors in the endometrium. Consequently, it was hypothesized that delivering a specific dose of hCG directly into the uterine cavity before embryo transfer could increase the likelihood of implantation.

 

Potential Mechanism of Action of Intrauterine hCG

hCG is not just a pregnancy hormone; it is an important messenger between the embryo and the uterus. In vitro studies have shown that hCG can:

• Stimulate the expression of certain molecules associated with endometrial receptivity.
• Regulate the activity of uterine immune cells, particularly uterine natural killer (uNK) cells.
• Alter the production of cytokines associated with implantation.
• Strengthen the initial communication between the blastocyst and the endometrium.

These findings led to the belief that administering hCG prior to embryo transfer could mimic the natural uterine environment of early pregnancy.

 

Early Studies and the Rise of Clinical Hope

In past years, several small studies and early meta-analyses reported that intrauterine hCG infusion might increase clinical pregnancy rates and even live birth rates. Some of these studies reported improvements in:

• Implantation rates
• Clinical pregnancy rates
• Ongoing pregnancy rates

For instance, early meta-analyses suggested that intrauterine hCG might be beneficial in certain IVF/ICSI cohorts. However, these studies were largely limited by small sample sizes, variations in hCG dosage, timing of administration, methodological quality, and high heterogeneity between studies. As a result, while the initial findings were promising, it remained unclear whether this effect was real or merely an artifact of study design limitations.

 

The New 2026 Human Reproduction Update Study: Reassessing Intrauterine hCG

The most critical new evidence in this area comes from a study titled:

Intrauterine human chorionic gonadotropin administration before embryo transfer (IHABT): an individual participant data meta-analysis of randomized controlled trials

which was published in the journal Human Reproduction Update in 2026.

Unlike conventional reviews, this study utilized an Individual Participant Data (IPD) meta-analysis approach, meaning individual patient data from various trials were gathered and re-analyzed. This methodology allows for a more precise evaluation of the treatment's effect across different patient subgroups.

In this analysis:

• 28 randomized controlled trials (RCTs) were identified.
• 7 studies with individual participant data involving 2,244 patients were included in the primary analysis.
• Most of the included studies with individual data were of high quality and had a low risk of bias.

The main finding was highly significant: Intrauterine hCG infusion prior to embryo transfer did not increase live birth or clinical pregnancy rates.

Statistical results showed:

• Live Birth: Odds Ratio = 0.99 (meaning there was virtually no difference compared to the control group).
• Clinical Pregnancy: Odds Ratio = 1.04 (no statistically significant increase).

 

Why Were Previous Study Results Different?

One of the crucial insights of this paper was investigating why previous study results differed. The researchers observed that studies lacking individual participant data often reported a significant increase in pregnancy rates; however, many of those studies lacked sufficient scientific credibility.

In other words, some of the previous positive results may have been influenced by:

• Small sample sizes
• Selective reporting of outcomes
• Protocol discrepancies
• Publication bias

This carries an important message for reproductive medicine: The promising initial results of an IVF add-on do not always translate to proven, real-world clinical benefits.

 

Does Any Specific Subgroup of Patients Benefit from Intrauterine hCG?

One of the primary goals of the new study was to determine if a specific subgroup of patients might respond better. Subgroups analyzed included:

• Recurrent Implantation Failure (RIF)
• Frozen embryo transfer (FET)
• Advanced maternal age
• Blastocyst transfer
• Use of IVF vs. ICSI

However, no convincing evidence was found to support the existence of any specific subgroup that benefits from intrauterine hCG. Therefore, under current conditions, intrauterine hCG cannot be recommended as a targeted treatment for any specific patient cohort.

 

Clinical Implications for Gynecologists and Infertility Specialists

These findings offer several key practical insights:

1. Reducing the Routine Use of IVF Add-ons: In recent years, numerous auxiliary methods have been introduced to boost IVF success. However, every new method must be evaluated based on critical outcomes like live birth rates, rather than just improvements in intermediary laboratory markers.
2. The Importance of Evidence-Based Treatment: If a treatment incurs additional costs, requires extra intervention, and shows no proven increase in live birth rates, it should not be offered routinely.
3. The Importance of Proper Patient Counseling: Many patients assume that adding more treatments always increases their chances of success. The physician's role is to explain that in IVF, the quality of evidence is far more important than the quantity of technologies utilized.

 

Conclusion

Intrauterine hCG infusion prior to embryo transfer was once one of the most appealing auxiliary methods in IVF, possessing a plausible biological rationale based on hCG's natural role in embryo-endometrial communication. However, newer, higher-quality evidence demonstrates that this method does not increase live birth or clinical pregnancy rates in the general IVF population.

Consequently, based on current evidence, intrauterine hCG should not be offered as a routine IVF add-on in fertility treatment. The future of assisted reproductive technology must move toward precise patient selection, personalized treatment, and the utilization of interventions with proven clinical utility in increasing live birth rates.

 

Brief References

• Zou H, et al. Intrauterine hCG administration before embryo transfer: IPD meta-analysis of RCTs. Human Reproduction Update. 2026.
• Murugesu S, et al. Intrauterine hCG at blastocyst transfer: systematic review and meta-analysis. J Gynecol Obstet Hum Reprod. 2023.
• ASRM Practice Committee. Evidence-based evaluation of IVF add-ons.