Fetal therapy, also known as in-utero treatment, represents a new level reached in modern medicine with the support of advancing medical technology. Recent developments in the diagnosis of fetal conditions have also provided deeper insight into how these conditions progress if left untreated.Today, we are much more informed about whether it is better to wait until after birth to treat a condition or to intervene while the baby is still in the womb. As a result, it is now understood that in certain cases, treating a condition before birth can lead to significantly better outcomes compared to postnatal treatment. In some situations, the chance of survival for the baby is considerably lower if in-utero treatment is not performed. Therefore, fetal therapy is not only preferred due to its potential to yield better results than postnatal treatment, but also because it can increase the likelihood of the baby's survival.
Today, not all conditions diagnosed in the womb have an available in-utero treatment option. However, in certain cases, fetal therapy has come into focus in modern medicine — especially when it has been shown to increase the baby's chances of survival and/or offer better outcomes compared to treatment after birth.
Anne karnında tedavi her koşulda herkes tarafından gerçekleştirilebilecek bir tedavi yöntemi değildir.Tedaviye başlamadan önce sorunun tam olarak ne olduğu ortaya konmalıdır. Bu amaçla ultrasonografi, MR, gerekirse amniyosentez ve benzeri işlemler yapıldıktan sonra sorun tam olarak tanımlanmalıdır. Tanı konulduktan sonra bu aşamada anne karnında tedavi yapmak mı doğru olacaktır, gözlem yapmak mı yoksa gebeliği sonlandırmak mı ya da tedaviyi doğumdan sonraya bırakmak mı en uygun yöntem olacaktır? Bu seçeneklerin hepsi birden fazla uzmanlık alanında kişilerin katılımıyla oluşan konseylerde (multidisipliner yaklaşım) aile ile birlikte tartışıldıktan sonra mevcut durumda anne karnında tedavinin daha uygun, daha yararlı ve fayda risk bakımından daha iyi olduğu anlaşılır ise o zaman anne karnında tedavi için plan yapmak gerekecektir.
Fetal therapy must be performed in advanced hospital settings, not in standard outpatient clinic conditions. Such a center should not only include a perinatology specialist, but also involve experts from other relevant medical fields based on the baby's condition. For example if the baby requires anesthesia, a pediatric anesthesiologist experienced in fetal procedures must be part of the team. Depending on the issue, the team may also include specialists in pediatric surgery, pediatric urology, pediatric neurosurgery, or other relevant disciplines. In short, fetal therapy requires a multidisciplinary team within a highly specialized medical center to ensure the highest level of care and safety for both mother and baby.
Before performing a fetal therapy procedure, the medical team must carefully document and include every detail in the treatment plan. All potential complications that may arise during the procedure should also be anticipated, and necessary preparations must be in place. Since post-procedure care involves monitoring both the mother and the baby, the healthcare personnel involved in follow-up at the treatment center must be specifically trained and experienced in this field. Having a well-prepared and skilled support team significantly contributes to the overall success and safety of fetal therapy.
Below are some of the conditions that are currently subject to in-utero surgery in modern medicine, or are being studied as potential candidates for such interventions — where fetal surgery is expected to offer benefit.
Traditionally, twin pregnancies account for approximately 1% of all pregnancies. Although they are seen more frequently today due to assisted reproductive technologies like IVF, the natural occurrence rate remains around this figure. About two-thirds of twin pregnancies have two separate placentas, while the remaining one-third share a single placenta between the two babies. In these cases, although each baby has its own umbilical cord, they both rely on a single placenta for nourishment.
Within a shared placenta used by both babies, vascular anastomoses—abnormal blood vessel connections—can form, allowing blood from one twin to flow into the circulation of the other. Because of these vessel connections, the donor twin gradually transfers blood to the recipient twin. As this process continues: The donor twin begins to shrink in size, has significantly reduced amniotic fluid (oligohydramnios), and appears growth-restricted. And the recipient twin, on the other hand, receives excess blood, leading to increased blood volume, becomes larger, has excess amniotic fluid (polyhydramnios), and the heart is forced to work harder to circulate the extra blood. As the imbalance progresses, the recipient twin's heart may eventually become overwhelmed, resulting in heart failure and fetal death. Following the death of the recipient twin, the donor twin is also at high risk, and if no intervention is made, both babies may be lost in utero.
The condition described above is known as Twin-to-Twin Transfusion Syndrome (TTTS) in twin pregnancies. After diagnosis, the syndrome is staged, and if the condition reaches a certain stage where in-utero surgery is likely to be beneficial, the babies become candidates for fetal surgery. During this in-utero procedure, which is performed under hospital and operating room conditions, the mother is brought to the operating theatre and usually given regional anesthesia. Using a special camera system called a fetoscope, the surgeon enters the amniotic sac and visualizes the blood vessels that are transferring blood from one baby to the other. With the help of laser technology, these abnormal vessels are cauterized to stop the blood flow between the two fetuses, preventing the imbalance from continuing.
The procedure is generally successful and has been shown to be beneficial in terms of outcomes compared to cases where no intervention is performed.For this reason, fetoscopic laser surgery is currently recommended worldwide as a treatment option for families whose babies are at the appropriate stage of Twin-to-Twin Transfusion Syndrome (TTTS).
As with any fetal surgery, this procedure also carries inherent risks. These may include the loss of one or both babies, premature rupture of membranes, preterm labor, the possibility of the procedure being unsuccessful, the need for a repeat procedure, the development of a condition known as pseudo-amniotic band syndrome, and, although rare, complications such as cerebral palsy.
Another condition in unborn babies that can be diagnosed during pregnancy and may potentially benefit from in-utero treatment is narrowing or obstruction at the outlet of the lower urinary tract. Like us, babies also produce urine in the womb using their kidneys. The urine produced by the kidneys flows through channels called ureters into the bladder (mesane). As the bladder fills, urine is released into the surrounding space, forming what we call amniotic fluid.This amniotic fluid plays a vital role—not only allowing the baby to move freely but also supporting the development of the lungs, preventing compression of the umbilical cord, and thus enabling the transfer of nutrients and oxygen to the baby, while also allowing waste products to be carried away via the mother. If there is an obstruction at the bladder outlet, urine cannot be expelled from the bladder, leading to a reduction in amniotic fluid. In such cases, the umbilical cord may become compressed, causing a lack of oxygen and potentially leading to fetal death. In addition, insufficient amniotic fluid can impair lung development, which may result in respiratory failure and death after birth. In babies who survive the pregnancy or immediate postnatal period, urine that accumulates in the bladder may flow backward to the kidneys, causing damage to the kidney cells (nephrons). This can lead to kidney failure after birth, requiring dialysis or even kidney transplantation. Due to these potentially life-threatening consequences, bladder outlet obstructions in unborn babies are considered fatal beyond a certain stage and may lead to the consideration of fetal therapy.
Bladder outlet obstructions in babies are generally classified into three main groups.
Urethral atresia is the complete absence of development of the urethra, the structure responsible for carrying urine from the bladder to the outside. This condition affects both female and male babies. Although shunt procedures can be performed in the womb, the outcomes are generally fatal.
This condition has been reported exclusively in male infants. In these cases, the urethra, which normally allows urine to exit the bladder, is present. However, a band-like structure at the point where the urethra exits the bladder obstructs the flow, preventing urine from being expelled properly. As a result, urine accumulates in the bladder and continues to back up toward the kidneys. On one hand, this backward pressure damages the kidneys; on the other hand, the reduced amniotic fluid can lead to compression of the umbilical cord, resulting in fetal death. If the baby survives the pregnancy, the lack of amniotic fluid may impair lung development, causing the baby to die after birth from respiratory failure. Even in cases where respiratory failure is avoided, these babies often face a future need for dialysis or kidney transplantation due to kidney damage.
Urethral stricture is another condition that can cause bladder outlet obstruction. In this case, urine from the baby's bladder is usually able to pass through, but only in very small amounts due to the narrowing. As a result, urine accumulates in the bladder and may cause complications similar to those described above, although generally to a less severe extent.If enough urine can exit to maintain a sufficient level of amniotic fluid, the likelihood of complications such as impaired lung development is considered to be lower.
The diagnosis of LUTO (Fetal Lower Urinary Tract Obstruction) is typically made at the end of the first trimester or the beginning of the second trimester of pregnancy. During a routine prenatal ultrasound, signs such as an enlarged bladder, urine backing up into the ureters, and dilation of the renal pelvis (the area of the kidney where urine collects) can clearly indicate LUTO. If the condition is due to a posterior urethral valve (PUV), a narrowing near the bladder outlet may be observed. This creates a characteristic appearance known as the "keyhole sign" on ultrasound. All of these cases occur in male fetuses. Additional findings may include reduced amniotic fluid and dilated renal pelvises in the kidneys, showing that urine is not being properly expelled.
In urethral atresia cases, the characteristic "keyhole sign" described earlier is not seen on ultrasound. Instead, the bladder appears completely distended, like a balloon. The renal pelvises (where urine first collects in the kidneys) are dilated, and amniotic fluid is always reduced.In cases of urethral stenosis, the bladder also appears enlarged. However, if the narrowing occasionally allows urine to pass, the amniotic fluid level may appear normal on ultrasound.
After a diagnosis of lower urinary tract obstruction (LUTO) is made during pregnancy, several important factors are carefully evaluated: the type and severity of the obstruction, whether the baby has any additional structural or genetic abnormalities, and whether there is a reduction in amniotic fluid. Babies with lower urinary tract obstructions are at a higher risk of having accompanying structural or genetic anomalies compared to other fetuses.
In cases of urethral atresia, where the urethra has not developed at all, the prognosis is extremely poor, even if surgery is performed in the womb. For this reason, atresia cases are generally not considered candidates for fetal surgery.
In cases of urethral stenosis, surgery is generally not considered as long as the narrowing still allows urine to pass and the amniotic fluid level remains normal. However, if the amniotic fluid begins to decrease, in-utero surgery may be considered, depending on a careful evaluation of the potential benefits and risks.
Posterior urethral valve (PUV) cases are the most commonly selected candidates for in-utero surgery. Before planning the procedure, it is essential to confirm that there are no additional genetic or structural abnormalities. Although evaluating anomalies via ultrasound can be challenging when amniotic fluid is low, every effort and available technique should be used to achieve an accurate assessment. If no other abnormalities are detected, the baby may be considered a suitable candidate for fetal surgery.
When making the decision to perform in-utero surgery, the staging or grading systems used can vary. Some medical teams assess whether the baby's kidneys are functioning by analyzing fetal urine samples, performing ultrasound evaluations of kidney damage, and considering the amount of amniotic fluid collectively.However, in recent years, some groups have adopted a different approach: once an obstruction is detected, they proceed directly with surgery, aiming to begin treatment as early as possible. The goal of this approach is to maximize the chance of preserving functional kidney tissue, thereby reducing the baby's future need for dialysis or kidney transplantation. Naturally, this strategy also means that more babies may be exposed to the risks of fetal surgery. Therefore, the benefits and risks of each approach should be carefully weighed, taking into account the family's expectations, and the decision should be made within a multidisciplinary team and in collaboration with the family. It is important to remember that for babies who undergo surgery, zero risk and 100% success do not exist. The nature of these procedures includes the possibility of failure, as well as complications such as pregnancy loss, premature rupture of membranes, preterm delivery, or damage to surrounding organs caused by the procedure (e.g., during laser intervention). Even in successful cases, there is no definitive data showing that the surgery will completely eliminate the baby's lifelong risk of dialysis or kidney transplantation. For these reasons, decisions about fetal surgery must consider all these factors. Based on the gestational age, the options of pregnancy termination, observation, or in-utero surgery should be evaluated thoroughly in terms of risk-benefit balance before a final decision is made.
After a LUTO diagnosis is made during pregnancy and a decision is taken to proceed with in-utero surgery, two main surgical methods come to the forefront:
1. Vesicoamniotic Shunt
2. Fetal Cystoscopic Laser (Fetoscopic Laser Ablation)
This was the method commonly used before laser procedures became widespread. In this technique, a vesicoamniotic shunt is placed to allow the urine—unable to exit the bladder—to drain. One end of the shunt is positioned inside the baby's bladder, and the other end remains outside the baby's body, within the amniotic fluid. The shunt remains in place until birth. The success rate of the procedure is approximately 60–70%, but one of the most problematic issues has been the displacement or blockage of the shunt, often requiring it to be replaced, which is highly undesirable. The procedure is performed under operating room conditions, where the mother is given local or regional (spinal) anesthesia, and the baby receives anesthesia and a muscle relaxant. The shunt is inserted under ultrasound guidance. Even if the procedure is successful and the baby survives, the risk of postnatal dialysis still remains. Therefore, close follow-up after birth is essential.
This is a surgical procedure made possible by modern technological advancements in medicine. Performed under operating room conditions, the mother receives regional (spinal) anesthesia, while the baby is administered anesthesia and muscle relaxants. A small camera (fetoscope) is then inserted into the baby's bladder to directly visualize the obstruction. Thanks to this camera view, it becomes possible to clearly differentiate whether the cause of the obstruction is PUV (Posterior Urethral Valve), urethral atresia, or urethral stenosis. If the problem is stenosis, a catheter can be placed into the urethra to allow urine to flow. If the issue is PUV, the procedure continues with laser ablation. Using laser fibers, the valve causing the obstruction is destroyed, creating a passage for urine to flow. The success of the procedure is confirmed by visualizing the flow of urine from the urethra into the amniotic cavity using Doppler imaging. Once proper urine flow is observed, the procedure is concluded. Following the procedure, the mother is typically hospitalized for observation on the same day due to potential risks. If no complications arise, she is usually discharged the next day.
Even in fetal cystoscopic laser procedures, there is no such thing as 100% success or zero complications. According to published case series, the success rate of the procedure is reported to be around 75%, and approximately 25% of these cases may still go on to develop kidney failure later in life. Unwanted outcomes such as procedure failure, premature rupture of membranes, pregnancy loss, and damage to surrounding organs are known risks associated with this intervention.
In conclusion, in certain cases of lower urinary tract obstruction (LUTO) in unborn babies, in-utero surgery may offer significant benefits. The selection of appropriate candidates, the evaluation of potential benefits, and the assessment of risks and possible complications must all be carried out through a multidisciplinary approach, in close collaboration with the family. All available options—including pregnancy termination, close observation, and fetal surgery—should be thoroughly discussed, and only then should a decision be made regarding the most appropriate course of action.
