Introduction

Cryotherapy is a time proven ablative method of treating lower grades of cervical dysplasia. Women who need cryotherapy typically have had an abnormal Pap smear which has led to colposcopy, biopsy, and a diagnosis of cervical dysplasia. The procedure is easy to learn and perform and can easily be applied in outpatient settings.

The device consists of a gas tank containing non-explosive, non-toxic gases (usually nitrous oxide but may be carbon dioxide). ^{1, 2} A 20 lb gas cylinder is preferable to the 6 lb "E" type tank since it has a more efficient pressure release curve. ² Liquid nitrogen has been used in the past but is difficult to control and is not currently recommended. ⁹ The regulator usually contains a gas cut-off and a pressure gage. The refrigerant is delivered via flexible tubing through a gun-type unit to the cryoprobe. Cryoprobe should be disinfected between uses, usually by chemical methods.

The cryoprobe is cooled by the Joule-Thomson effect. The refrigerant gas is fed into the hollow cryoprobe under pressure. The gas then rapidly expands and absorbs heat in the process. This reduces the temperature of the probe of nitrous oxide based units to -65 to -85 degrees Centigrade. The cryoprobe then acts as a heat-sink and removes heat from the cervical tissue. ²

After the cryoprobe is placed in contact with the cervix and activated, a ring of frozen tissue or "iceball" rapidly moves outward. The depth of freeze approximates the lateral spread of the freeze. Most of the tissue in this zone will necrose. However there is a ring of tissue (the thermal injury or recovery zone) that freezes but doesn’t reach the -20 degrees necessary for cell death. ³ This is why it is necessary to freeze well beyond the margins of any lesions.

Studies have demonstrated that endocervical crypt (gland) involvement of cervical intraepithelial neoplasia (CIN) may penetrate up to 3.8mm into the cervix. ⁴ Therefore, a freeze that causes cell death to 4mm will effectively eradicate 99.7% of lesions with gland involvement. Current recommendations are to produce an iceball with a 5mm lateral spread to accomplish this goal.

A water soluble lubricant is applied to the probe to act as a thermocouple with the irregular surface of the cervix. ¹ This produces a more uniform freeze. A rapid freeze followed by a slow thaw maximizes cryonecrosis. ^{2, 5} A freeze-thaw-refreeze cycle is also more effective than a single freeze. ^{2, 6, 7, 1, 8}

Often reserved for CIN 1 and 2 level lesions. There may be a higher recurrence rate compared to LEEP for CIN 3 level lesions, possibly due to the greater depth of glandular involvement with CIN 3. ^{8 -11}

Indicated for disease limited to a small area of cervix that is easily visible in its entirety. The cryotherapy probe must be able to cover the entire transformation zone and the entire lesion for the therapy to be most effective.

• Lesions extending into the endocervical canal more than a few millimeters since the area of destruction may not reliably penetrate beyond this level. A positive endocervical curettage is also a contraindication. Another modality of treatment should be considered in these situations. ^{1, 9, 12, 13, 14}
• The cytologic, histologic, and colposcopic findings should be consistent within 2 histologic grades.
• Although case reports report no associated complications, cervical cryotherapy should be avoided in pregnancy.
• Large lesions that can not be covered with the cryoprobe. 1
• Active cervicitis
• Some authors recommend using an excisional therapy (such as LEEP) for recurrent dysplasia after ablative therapy. ⁹
• CIN 3, CIS, or Invasive lesions. ⁷
• Adenocarcinoma-in-situ.

• Serious injuries or complications are rare.
• It is quick and easy to learn and to perform.
• It can be done easily in the outpatient setting with relatively simple and inexpensive equipment.
• No anesthetic is required. The procedure is relatively painless although cramping may occur. Some authors recommend the use of NSAIDS to decrease cramping ^{15, 16} or submucosal injection of 1% lidocaine with 1:100,000 epinephrine to decrease local pain. ^{16, 17}
• It can be performed in a short time and does not interfere with other activities such as work or school later in the day.
• There is minimal chance of heavy bleeding during or after the procedure.
• It is the least expensive widely available form of treatment for CIN.
• There is apparently little effect on fertility or labor. ⁹

• Women will experience a heavy discharge for several weeks after cryotherapy. ^{9, 18, 19, 20} Amino-Cerv cream ( 1 applicator high in the vagina Qhs for 10 days) may be used after therapy in an attempt to decrease the discharge.
• Uterine cramping often occurs during therapy but rapidly subsides after treatment. ^{18, 19, 20}
• Bleeding and infection are rare problems during the reparative period. ¹⁸
• Cervical stenosis may occur following cryotherapy.
• Unlike excision therapies, there can be no histologic examination of the entire lesion. ⁹ However, the cost of histologic examination is saved.
• Future Pap smears and colposcopy may be more difficult after cryotherapy. The squamocolumnar junction has a tendency to migrate deeper into the cervical os making it difficult to sample the endocervix. ^{9, 20} This is especially true of older "nipple-tipped" probes that are not currently recommended.
• Failure of therapy ²¹

• The appointment should be scheduled when the patient is not experiencing heavy menstrual flow.
• She may take ibuprofen, ketoprofen or naproxen sodium before cryotherapy to decrease cramping.
• Informed consent is obtained listing risks and benefits as noted above.
• If there is any doubt about the patients pregnancy status, a pregnancy test should be performed.
• Check to make sure that there is adequate pressure in the tank (usually the needle will be in the "green zone" on the pressure gage.)
• Place the patient in the dorsal lithotomy position. Select the largest speculum that the patient can comfortably tolerate, and open the blades and the front end of the speculum as widely as possible without discomfort. If collapsing side walls are a problem, place a condom with the tip cut off, the thumb from a very large rubber glove with the tip cut off, or half of a penrose drain over the speculum. Alternatively, tongue blades or side-wall retractors may be placed to improve exposure.
• Select a probe that adequately covers the entire lesion and the entire transformation zone. Use only flat-ended probes, not probes with long endocervical extensions or "nipple-tipped" probes. Apply a water soluble lubricant to the probe to act as a thermocouple with the irregular surface of the cervix.
• Apply the probe firmly to the cervix and make sure that it is not touching the side walls of the vagina. Start the freeze by pulling the trigger (green gun) or pressing the freeze button (black gun). Within a few seconds the probe will be frozen to the cervix, and the cervix can then be gently drawn forward a few millimeters into the vagina where probe contact with the side walls is less likely. A rim of ice should form and grow to a width of at least 5mm in all quadrants. The older method of using a 3 minute freeze (followed by a 5 minute thaw then a 3 minute freeze) may also be used. ^{1, 9}
• Discontinue the freeze. On the green gun release the trigger and on the black gun press the defrost button. Wait until the probe visibly defrosts to disengage it. The cervix should be allowed to regain its pink color (usually over about 5 minutes.)
• Repeat the freeze sequence as above. The second time is usually faster. After the freeze is completed, disengage the probe and remove the speculum. The patient may get up, get dressed and leave as soon as she is ready.

The most common minor complication to occur is for the probe to touch the vaginal side wall and to adhere to it. This will cause pain. The operator may quickly push the vaginal mucosa off the probe with a tongue blade. If this is not done quickly it will become more difficult as the freeze deepens, and more vaginal mucosa will be destroyed. The operator should defrost the probe just enough to release the side-wall and then continue the freeze. Slight bleeding may occur from the injured vaginal mucosa. Occasionally a tongue blade placed along each side wall as a barrier is the only way to prevent unwanted contact between the probe and the vagina.

A second possible problem is an asymmetric freeze on the face of the cervix. Changing probes or freezing in segments will usually solve this problem.

Occasionally a patient may experience an undue amount of pain and cramping, usually associated with a high level of anxiety. If this can be anticipated, a paracervical block prior to cryotherapy, IM benzodiazapines (ie 1mg Ativan IM) or IV sedation may be chosen for relief. These measures will rarely be required. Rarely a patient may have a vasovagal reaction. Allow the patient to rest on the examination table after the procedure and to get up slowly is usually sufficient to overcome this problem.

Most patients experience a heavy and often odorous discharge for the first month after cryotherapy. This discharge results from the sloughing of dead tissue and exudate from the treatment site. Some physicians recommend debridernent of the eschar to decrease the discharge although this has not been proven to be effective. Aminocerv cream may be prescribed if a heavy discharge is present post-procedure.

The patient should refrain from sexual intercourse and tampon use for 3 weeks after cryotherapy to allow the cryotherapy bed time to reepithelialize. Excessive exercise should likewise be discouraged to lessen the chance of post-therapy bleeding. 9, 19

The first follow-up Pap should be done in 3 to 6 months. A Pap smear is of no value during the sloughing or regenerative phases which takes at least 3 months to complete. If this and the following smears are normal, Pap smears should be repeated every six months for two years from treatment. Most recurrences will occur within 2 years of treatment. ⁹ Yearly smears may be recommended after that. An alternative method involves replacing the initial and each yearly Pap smear with a colposcopic examination. If any of the follow-up tests are positive, restart the work-up as if there was a new, first-time dysplasia.

If a follow-up Pap smear is abnormal, a colposcopy with directed biopsy is usually performed. Unfortunately, colposcopy may be more difficult due to migration of the squamocolumnar junction deeper into the cervical os. Other treatment methods (usually LEEP) are preferred if persistent disease is discovered.

Click here for selected outcome studies of cryotherapy for the treatment of cervical dysplasia from the English language literature.
Click here for physician charges for treatments for cervical dysplasia.

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