Monday, January 28, 2013

All you wanted to know about embryo transfer

The day when our in-vitro embryos return back to us (to their mama !) is one of the most exciting moments of an IVF cycle. We forget the struggles we went through when we are admiring our microscopic babies under the microscope. Embryo transfer is one of the rate-limiting steps in an IVF cycle and plays a pivotal role in determining IVF success. Since the invention of IVF, major developments have been made in ovarian stimulation protocols; the way oocytes are collected ; and in the IVF lab; but the embryo transfer method remains largely unchanged. Embryo transfer done badly by an inexperienced doctor can change the fate of an IVF cycle –there is a vital intangible “physician factor” involved in determining the outcome of an IVF cycle! When different individuals perform embryo transfer within the same ART programme , the pregnancy rate of each doctor varies widely. This shows the importance of the embryo transfer technique and how it determines IVF outcome. It is estimated that 30% of IVF cycles fail because of shortcomings in this crucial procedure. What actually happens during an embryo transfer ? Is it an easy procedure ? Will it be painful ? Can my embryos fall out of my uterus after the transfer ? As usual there are many questions: come let us find the answers together.

What is an Embryo Transfer ?


Transferring one or more embryos into the uterine cavity of the recipient is called embryo transfer (ET).  It is the final and crucial step of an IVF process. The embryos in the IVF lab are grown usually until day 3 or day 5 in an incubator in a petri dish. The quality of embryos are graded by inspection under a microscope. The top quality embryo(s) are returned back to the uterus , where they belong ! Even though more than 90% of patients who undergo IVF reach the embryo transfer stage , only a small percentage of them actually get pregnant. Unfortunately, not all the embryos which are transferred to the uterus become deeply desired babies !


How is an ET performed ?


During ET, the doctor puts you in the undignified lithotomy position in the OR, and inspects your cervix with the help of a speculum . The sticky cervical mucus is cleared away using a moist cotton swab carefully. Then the cervix is washed with a sterile fluid. The best embryos are then loaded into the transfer catheter ( a long thin hollow soft sterile plastic tube) by the embryologist in the adjoining IVF lab . He does this under the microscope, and sucks up the embryos into the catheter by applying negative pressure with the help of a 1 ml syringe.  He brings the loaded catheter to your doctor , who performs the ET slowly by inserting the catheter into the uterine cavity through the cervix;  and then expelling its contents ( which consist of the embryos floating in a microscopic drop of culture medium)  by gently pushing the barrel of the syringe. This deposits the embryos into the cavity of your uterus. This method of transferring embryo(s) to the uterus is called transcervical  (through the cervix) embryo transfer. After transferring the embryos , the doctor hands over the catheter to the embryologist , who then examines it immediately under the microscope, to see whether there are any embryo(s) retained in the catheter. If this is the case, the retained embryo(s) are transferred back again to the recipient. An embryo transfer procedure is normally painless, and takes only few minutes to perform. You do not need anesthesia for this procedure. Most embryo transfers are easy but some embryo transfers can be difficult too ! Normally your husband is allowed to stay with you during the ET procedure , in order to hold your hand and provide you with emotional support , so that you remain stress-free and relaxed.

Are there any variations in the transcervical embryo transfer method ?


Transcervical embryo transfer is performed in two ways – without ultrasound guidance (traditional ‘clinical touch’ method) and with ultrasound guidance.
In the traditional ‘clinical touch’ method , the catheter is positioned blindly in the “desired position” ( about 1 to 2 cm away from the uterine fundus), by relying on the clinician’s tactile senses. In other words the ‘clinical touch’ embryo transfer method relies on the experience of the person who transfers the embryo ! During ultrasound-guided embryo transfer, the clinician is able to find the appropriate position for placing the catheter and releasing the embryos using the ultrasound scan image. During ultrasound-guided embryo transfer , you need to have a full bladder , so that the uterus can be viewed clearly ! It does create a lot of discomfort for the patient because the embryo transfer procedure can cause pressure on the already full urinary bladder ! The uterus should not be disturbed during the transfer in order to avoid uterine contractions – if the uterus contracts,  there is a danger of the embryo being expelled from the cavity.


Is ultrasound-guided embryo transfer better than ‘clinical touch’ method ?


As usual , this is a hotly debated topic. There are studies which reported that ultrasound-guided embryo transfer significantly enhanced embryo implantation rates ; and there are studies which found no difference if the ET was done by an experienced clinician in the absence of ultrasound guidance. This is a decision which is best made by your doctor , based on what works best for him ! For junior doctors, an ultrasound guided transfer seems better, as they learn how to master this procedure.


What are trial transfers or mock embryo transfer?


Trial transfers or dummy transfers are performed before the actual embryo transfer. They can be done just before the ET ; or during the ovum pick-up ; or prior to the start of the IVF cycle. During a trial transfer the doctor inserts an empty catheter into the uterine cavity , to find the easiest passage to the cavity; and to measure the length of the uterus and the cervical canal (uteri and cervixes come in many different shapes and sizes !) This allows him to measure how deep he has to insert the catheter , so that he can place the embryo at the appropriate position inside the uterus , without disturbing the fundus. Most embryo transfers can be performed easily , but there are some women where the doctor finds it technically difficult to negotiate the catheter through the cervix. In such a situation , their cervix has to be dilated to widen the cervical canal , so that the embryo transfer catheter passes easily through the cervix. There are women where the doctor needs to use a tenaculum to straighten the uterine axis (remember that the cervical canal and uterus are at an angle to each other) and sometimes the uterus is so tilted that the passage of the catheter from the internal opening of the cervical canal into the uterus is difficult. Sometimes pulling on the tenaculum alone cannot do the job , especially if the uterus is acutely angulated in relation to the cervical canal. Then it maybe necessary to curve the catheter, so it conforms to the curve of the uterus. In these patients, using specially designed catheter sets allows the doctor more freedom in gently guiding the catheter through the cervix.


What factors play a role in affecting embryo transfer results ?


The embryo transfer should be smooth and trauma-free. Many studies have shown that the pregnancy rate after embryo transfer is better if it is performed by an experienced physician, as compared to a newbie.
1.    Placement of the embryo
Placing the embryo 2 cm from the uterine fundus (the upper rounded extremity of the uterus , above the openings of the fallopian tubes) helps in enhancing embryo implantation. This is the region which is thought to possess maximum implantation capacity.
2.    Uterus contraction
When the cervix is handled roughly or if the catheter touches the uterine fundus , the uterus can contract. This can expel the embryos from the uterine cavity into the fallopian tubes or cervical canal, and compromising IVF success.
3.    Cervical mucus
Carefully removing the cervical mucus without causing trauma to the cervix improves IVF outcome. The cervical mucus can plug the catheter tip , thus preventing the deposition of the embryo in the uterus. It can also be a source of introducing bacterial contamination into the otherwise sterile uterine cavity.
4.    Catheter choice
Soft catheters have a better IVF outcome because they avoid trauma to the uterine wall.
5.    After the doctor has done the transfer, the embryologist checks it under the microscope. The presence of blood in the catheter suggests that the transfer was technically difficult – and this may reduce pregnancy rates.
6.    Trapped embryos. Sometimes the embryos remain trapped with the catheter, even  through the doctor has plunged the barrel of the syringe completely. When the embryologist identifies the trapped embryos in his petri dish, he simple reloads them again into a new catheter, and the doctor can then re-transfer them . This does not seem to affect pregnancy rates.


Why are some embryo transfers difficult to perform ?


Some embryo transfers are difficult to perform because of the following problems in patients :
1.    Cervical stenosis ( narrowing) or anatomical distortion of the cervical canal and uterus
2.    Acute utero-cervical angulations


If a physician has several years of experience in doing IVF, then most embryo transfers are like a cakewalk. But in some women , the embryo transfer can become an arduous adventure because of the difficulty encountered in traversing the cervix. This is commoner in women of Indian and African origin , where pelvic inflammatory disease (PID) and cervical infections are more prevalent. There can also be anatomical distortion of the cervical canal and uterus because of previous surgery.  These conditions might lead to a traumatic embryo transfer (there might be bleeding , and the patient many experience pain) ; or the embryo transfer cannot be performed at all. The presence of an acute curvature between uterus and cervical canal (utero-cervical angulation) can also make the embryo transfer hard to perform.


How to avoid difficult embryo transfers ?


Performing mock transfers before the actual embryo transfer helps in identifying the problem beforehand , and can help the doctor to take precautionary measure. For example patients with cervical stenosis can undergo a process called cervical dilation to widen the cervical canal. This might help in the atraumatic passage of the ET catheter into the uterine cavity.
But there are some patients in which transcervical embryo transfer becomes impossible ! In such rare cases , there are other techniques which could be used to transfer the embryo to the uterus.


What are the methods which bypass the transcervical route for embryo transfer ?


1.    Transmyometrial embryo transfer
2.    ZIFT

Transmyometrial embryo transfer

In this method , using a special Towako set, two needles (one inside of the other) are passed through the vagina into the uterus wall , under ultrasound guidance, until the needle tip reaches the edge of the endometrial lining. The inner needle is then removed and a thin catheter is inserted inside the outer needle, which carries the embryo into the cavity. The embryos are then released in the endometrium. But the success rate with such embryo transfers are less when compared to transcervical embryo transfers.

ZIFT

ZIFT stands for zygote intrafallopian transfer. During ZIFT , cleavage stage embryos are transferred into the fallopian tubes , instead of the uterus , using laparoscopy. ZIFT is a very good option for women who cannot have a transcervical embryo transfer, but who have at least one normal fallopian tube. Since cleavage stage embryos belong to the fallopian tube and not to the uterus , ZIFT has a higher pregnancy rate than conventional ET.

Most clinics are not able to offer the option of doing a ZIFT , because of the lack of surgical skills and anesthesia facilities. If your embryo transfers are difficult, then find a clinic which offers this option !
 

e-SET

Elective single embryo transfer (e-SET) is becoming popular for women who are young and have good ovarian reserve. While transferring multiple embryos improves the pregnancy rate, it also increases the risk of multiple gestation. Children who are a result of multiple pregnancies have an increased risk of health problems, because of the increased risk of preterm delivery and low birth weight . With the advent of better embryo selection strategies such as comprehensive chromosome screening (CCS) , single embryo transfer may become the norm in the future !

This is an excerpt from our forthcoming, book, The Expert Patient's Guide to IVF. This being authored by our expert patient, Manju and me.

 You can email Manju at [email protected]

Her blog is at www.myselfishgenes.blogspot.com
 


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