Difficult embryo transfer: Challenges, techniques, and solutions – our experience

INTRODUCTION

Embryo transfer (ET) is a critical and technically sensitive step in the in vitro fertilization (IVF) process, directly influencing implantation and pregnancy outcomes. While most ETs are straightforward, approximately 5–7% are technically difficult and may adversely affect clinical success rates.^[1] Studies suggest that 17–34% of transfers are moderately complex, requiring minor adjustments, while 7–17% are classified as difficult, often necessitating additional interventions such as cervical dilation or tenaculum application.^[2]

Difficult ETs may involve anatomical abnormalities, technical complications, or patient-related factors that hinder smooth catheter navigation and embryo placement. This review explores the causes, challenges, and evidence-based solutions for difficult ETs, highlighting advanced strategies supported by recent studies and clinical publications as well as experience in our fertility clinic.

Difficult ETs are associated with reduced implantation and pregnancy rates. A recent meta-analysis reported a significant reduction in clinical pregnancy rates (odds ratio: 0.70; 95% CI: 0.64–0.76) in difficult ET cases.^[3] In addition, traumatic transfers may induce uterine contractions, further compromising implantation success.^[4]

These challenges may arise due to cervical stenosis, uterine angulation, anatomical abnormalities, or technical factors. Given the physical, emotional, and financial burden of IVF, optimizing the ET technique is essential.

This review aims to provide a structured overview of the causes of difficult ET, along with evidence-based strategies and practical solutions to improve clinical outcomes.

PRE-PROCEDURAL PREPARATION

Proper preparation plays a crucial role in minimizing the risk of difficult ET. A detailed patient history should be obtained, including prior intrauterine insemination, hysterosalpingography, previous ETs, pelvic surgeries, and any known uterine anomalies. Conditions such as pelvic inflammatory disease or Asherman’s syndrome may predispose to cervical stenosis and difficult catheter passage. In addition, endometrial polyps, uterine fibroids, or congenital abnormalities such as a septate uterus can obstruct smooth catheter passage.

A mock ET can be useful in identifying cervical alignment, uterine depth, and potential obstructions. While routine use before the first IVF cycle does not significantly improve pregnancy rates, it provides valuable anatomical insights that help guide subsequent procedures. Sueldo et al. emphasize that mock transfers significantly improve the accuracy and ease of the actual ET, thereby enhancing the overall success of assisted reproductive technology.^[5] A randomized controlled trial by Borkar et al. examined the impact of mock ET (MET) before the first IVF cycle. The study highlighted that while MET is often reserved for patients with a history of difficult transfers, its routine use before the first IVF attempt offers no significant improvement in clinical pregnancy rates. However, it provides valuable insights into uterine anatomy and potential challenges, allowing for a more tailored approach in subsequent cycles.^[6]

Ultrasound guidance has been shown to improve pregnancy rates and increase the likelihood of atraumatic transfers.^[7] A moderately full bladder facilitates better visualization by straightening the uterocervical angle; however, overdistension should be avoided as it may distort anatomy and cause patient discomfort.^[8] Figure 1 represents a full bladder required during ET.

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Figure 1: Transvaginal ultrasonographic image demonstrating a well-distended urinary bladder, the embryo transfer (ET) catheter positioned within the uterine cavity, and the echogenic air bubble marking the site of embryo deposition.

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Cervical preparation is equally important. Cleaning the cervix with sterile saline or culture media removes mucus, which may otherwise obstruct the catheter tip or lead to embryo retention.^[9,10] Figure 2 shows how the instrument trolley is set up to facilitate the process of ET.

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Figure 2: Instrument trolley set up during embryo transfer.

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For patients with a history of difficult or painful transfers, administering muscle relaxants or analgesics before the procedure can help reduce cervical resistance, making the transfer smoother.^[11] In cases where patients experience severe discomfort or anatomical challenges, general anesthesia may be necessary. In addition, pre-treatment with vaginal estrogen or cervical priming agents can soften the cervical tissue, making catheter insertion easier, particularly in patients with cervical stenosis or a rigid cervical canal.^[12]

CLASSIFICATION OF CHALLENGES IN ET

Difficulties encountered during ET can be broadly classified into:

Entry challenges

• Vaginismus,

• Narrow or stenotic cervical os,

• Posterior or Elevated cervix, and

• Vaginal or cervical obstruction as represented in Figure 3 showing a vaginal cyst blocking the entry of the ET catheter.

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Figure 3: A vaginal cyst blocking the embryo transfer catheter entry.

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MANAGEMENT OF DIFFICULT ET

Optimization of visualization

• Ultrasound guidance remains the cornerstone of accurate ET. Proper adjustment of depth, focus, and contrast improves visualization of the endometrial cavity and catheter tip. Performing the procedure in a dimly lit room further enhances image clarity. By carefully fine-tuning these ultrasound parameters, clinicians can significantly improve the precision and effectiveness of the ET procedure, leading to better clinical outcomes.^[9]

• Bladder filling should be optimized to improve the uterine axis without causing distortion. In obese patients or those with abdominal scars, probe positioning and angulation may need modification.

• Advanced techniques such as transvaginal ultrasound (TVUS) guidance can be particularly useful in patients with poor transabdominal visualization or complex anatomy. Figure 4 represents a TVUS-guided ET procedure.

• Measurement Technique: After positioning the outer catheter at the internal os, measure the distance to the maximum implantation potential and then place embryos accordingly at the point

• Feel Technique: When visualization is limited, estimate the uterine-cervical length (typically ~2.5 cm) and place embryos based on tactile feedback. While less precise, it remains an effective alternative in challenging cases.

• Echogenic Catheters: Echogenic catheters enhance the success of challenging ETs by improving visibility under ultrasound guidance. These catheters have echogenic markers or coatings, typically made of microbubbles or metallic particles, which reflect ultrasound waves, making the catheter tip more visible. This improved visualization is especially beneficial in patients with complex uterine anatomy, such as sharply anteverted or retroverted uteri, cervical stenosis, or tortuous cervical canals. Clear identification of the catheter tip ensures accurate embryo placement, while the observation of air bubbles entering the cavity confirms correct positioning, enhancing procedural precision and potentially improving pregnancy outcomes.^[13,14]

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Figure 4: Diagrammatic representation of the transvaginal ultrasound-guided embryo transfer procedure.

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Management of entry difficulties

Mild sedation or anesthesia may be considered in selected cases to reduce discomfort and facilitate cervical relaxation. Evidence suggests that anesthesia does not adversely affect pregnancy outcomes.^[15] A study conducted by Banerjee and Singla comparing ETs performed with and without anesthesia found no significant difference in success rates.^[15]

In cases of cervical stenosis, gentle dilation or the use of smaller or angled catheters may aid entry. A Sims speculum may provide better exposure compared to Cusco’s speculum in difficult cases. Stabilization of the cervix using a tenaculum or vulsellum can help align the uterocervical axis and facilitate catheter insertion. In our clinical practice, when the cervical opening is extremely narrow, a small incision may occasionally be performed to facilitate ET as shown in Figure 5. If minor bleeding occurs following the procedure, gentle pressure is applied to manage it effectively and maintain optimal conditions for implantation.

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Figure 5: Representation of an incision at the cervix with scalpel.

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When dealing with cervical obstructions, we have observed that using an outer catheter with a stylet can help navigate the blockage. It is essential to avoid applying excessive force, as it can damage cervical tissues and reduce implantation rates.

For patients with high or hard-to-reach cervices, we have observed that using angled catheters or Sim’s speculum can enhance access and simplify navigation. In cases of cervical stenosis, severe angulation, obesity, or poor visualization, gently stabilizing the cervix with instruments such as a vulsellum may be necessary to ensure proper embryo deposition.

Management of negotiation difficulties

Difficulties during ET often arise after entering the cervical canal, especially when navigating a curved or rigid uterine path. Several conditions can complicate this negotiation process.

A false passage in the cervix can occur when the catheter strays from the intended cervical path, often due to incorrect handling or excessive force. This misdirection may lead the catheter to move outside the cervical canal, complicating accurate embryo placement and potentially lowering implantation success rates. Occasionally, cervical stenosis or an acute angulation between the cervix and the uterus limits uterine access and makes ET difficult.^[16] This can make catheter navigation difficult. This condition creates resistance, making it harder to advance the catheter into the uterine cavity, requiring precise manipulation or specialized catheter types for successful ET.

A sharply anteverted or retroverted uterus can further complicate catheter placement by altering the cervical trajectory. This challenge can be managed using angled catheters or manual uterine adjustments during the procedure to improve alignment and facilitate smooth catheter passage.

Navigating the cervical canal and uterine cavity requires careful technique. Flexible or soft catheters are preferred in tortuous or angulated anatomy, as they reduce trauma and improve ease of passage.^[17,18]

Figure 6 represents the uterine anatomy by TVUS and the personalization of the ET based on anatomical characteristics of the uterus.

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Figure 6: Ultrasound-guided embryo transfer (ET) techniques in difficult anatomical scenarios. This figure illustrates the visualization of uterine anatomy by transvaginal ultrasound and the use of different catheter types tailored to specific anatomical challenges encountered during ET. Variations such as marked anteversion, tortuous cervical canal, crypts, and cesarean-induced ischioceles are addressed using soft, curved, and angled-tip catheters under ultrasound guidance to ensure accurate and atraumatic embryo placement. Reproduced from: Larue L. Evaluation of a strategy for difficult embryo transfers. Fertil Steril Rep. 2020. ©2020 Elsevier. Reproduced with permission.

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A slow, controlled approach should be adopted to avoid false passage formation. Ultrasound guidance combined with tactile feedback helps ensure correct catheter positioning.

In cases of significant resistance, switching to a firmer catheter or using a stylet may facilitate passage. However, excessive force should always be avoided.

STEPWISE APPROACH TO DIFFICULT ET

1. Difficult to negotiate with previous history

   1. Mock ET – A mock ET is a preparatory procedure performed before the actual ET to evaluate the cervical and uterine pathway. It helps identify potential difficulties and guides the selection of the appropriate catheter and technique. This improves the chances of a smooth and successful ET.

   2. Cervical dilatation and hysteroscopic correction: In cases of difficult ET due to cervical stenosis or tortuosity, various cervical dilation and hysteroscopic correction methods can be employed. Techniques include cervical canal shaving and dilation, refashioning of the cervical canal with Versa point,^[19] hysteroscopic evaluation combined with Malecot catheter placement, and hysteroscopic MyoSure morcellation to remove intrauterine obstructions, ensuring smoother and more effective ET. All these are done before the actual ET.

   3. Provisionally under general anesthesia – It helps by relaxing the uterine and cervical muscles, minimizing patient movement, and allowing the doctor to manipulate the cervix more easily. It reduces pain and discomfort, enabling a smoother and more controlled transfer, especially when resistance, cervical stenosis, or severe uterine angulation is present. At our center, we employ general anesthesia in select difficult cases and have found that it makes the procedure easier to perform and increases the likelihood of a successful transfer.

   4. Prophylactic oxytocin antagonist (Atosiban); A study by Moraloglu et al. suggests that treatment with oxytocin antagonists before ET may significantly enhance implantation rates in IVF cycles by reducing uterine contractility, thereby promoting better embryo adhesion and improving overall pregnancy outcomes.^[20]

2. In cases of incidental difficult ET with no previous history, several methods can aid in successful catheter navigation. Techniques include smooth movements, checking directions, and angulations, using a firmer catheter, or employing a stylet. Holding the cervix with a tenaculum to straighten the axis, gentle sounding, or trans myometrial ET may also facilitate the procedure difficult to negotiate without previous history.^[18] At our center, we have found that simply switching to a firmer catheter resolves the difficulty in most such cases, allowing for a smooth and successful transfer.

TECHNIQUES FOR EFFECTIVE ET

• Direct transfer: The embryologist loads the embryos, which are immediately transferred to the uterine cavity.

• Afterload technique: The outer catheter is positioned at the internal OS, and the inner catheter is subsequently loaded and inserted. This method minimizes embryo exposure time and ensures accuracy.

• The clinician performing the ET plays a pivotal role in determining its success. Their expertise, precision, and adaptability are essential, particularly in difficult cases. Skilled handling of complex anatomical challenges, precise catheter navigation, and the ability to make real-time adjustments significantly influence the accuracy of embryo placement. The human factor is a critical determinant of IVF success, as the clinician performing the ET significantly impacts the cycle outcome. Cirillo et al.^[21]

INNOVATIONS

Recent advancements in ET technology have improved procedural accuracy and success rates. The use of 3D and 4D ultrasound offers enhanced spatial visualization of the uterine cavity, helping clinicians detect abnormalities and optimize catheter trajectory. These imaging techniques are particularly helpful in identifying fibroids, endometrial polyps, or adhesions that could interfere with catheter placement. In addition, magnetic resonance imaging guidance is being explored for complex cases with severe anatomical distortions, providing detailed visualization of the pelvic structures.

CONCLUSION

Difficult ETs present significant clinical challenges, but careful preparation, appropriate technique, and the use of modern technology can optimize outcomes. A structured and individualized approach, combined with operator expertise, is essential to achieving atraumatic and effective ET. Continuous refinement of techniques and ongoing training remain crucial for improving success rates and enhancing patient experience in IVF.