2 The procedure
2.1.1 Menorrhagia is heavy cyclical menstrual bleeding over several consecutive cycles in a woman of reproductive years. Menorrhagia is clinically defined as a total menstrual blood loss of more than 80 ml per menstruation.
2.1.2 Menorrhagia has adverse implications for quality of life. Women with menorrhagia may have difficulties with daily activities such as work, family life and social activities. Many women report anxiety, depression, embarrassment and problems in their sex lives as a result of menorrhagia. Anaemia is also common among women with menorrhagia, and this may further impair quality of life.
2.1.3 Patients are usually treated with medication before surgery is considered. This may be administered orally or released into the lining of the uterus (endometrium) by a special intrauterine device. Historically, hysterectomy has been the standard surgical option for women with menorrhagia who no longer desire to maintain fertility. Alternatives to hysterectomy are minimally invasive procedures that may be performed using a hysteroscope. These include transcervical endometrial resection or destruction of the endometrium with lasers, electrocautery, radiofrequency waves or heated saline. Non-hysteroscopic procedures include destroying the endometrium using heated saline, heated balloons, lasers, radiofrequency waves or microwaves. Non-hysteroscopic procedures are often carried out under local anaesthesia as a day admission.
2.2.1 Endometrial cryotherapy is a non-hysteroscopic procedure that uses cold temperatures to freeze and destroy the endometrium. It can be performed under general, regional or local anaesthesia, although sometimes no anaesthesia is needed. A cryoprobe is inserted into the fundus of the uterus and cooled by perfusing it with either liquid nitrogen or a compressed gas mixture. The tip of the probe is placed first in one cornu of the uterus and then in the other, to generate an iceball that destroys the endometrial tissue. Each freeze cycle is followed by a heat (thaw) cycle, which allows the probe to be removed. Additional freeze/thaw cycles may be carried out if necessary.
2.3.1 In a randomised controlled trial (RCT), rates of treatment success as assessed by the reduction of menstrual bleeding to a pictorial blood loss assessment chart (PBAC) score of 75 or less in the absence of retreatment at 12 months were 67% (130/193 patients) and 73% (63/86 patients) in the cryotherapy and electroablation groups, respectively. The proportion of patients in the cryotherapy and electroablation groups at 12 months (not analysed by intention to treat) with menorrhagia (PBAC greater than 100) were 12.2% and 6.9%, respectively, and with amenorrhoea (PBAC score 0) were 27.6% and 55.6%, respectively. In a case series of 67 women, none were amenorrhoeic during more than 3 months of follow-up (up to 18 months).
2.3.2 Patient satisfaction ranged from 67% (22/33) at up to 18 months' follow-up in the case series, to 91% at 24 months in the RCT.
2.3.3 Retreatment at 24 months was reported for 10% (18/186) of patients who had cryotherapy in the RCT: 7% (13/186) of patients had a hysterectomy and 3% (5/186) of patients had repeat cryoablation. For more details, refer to the Sources of evidence.
2.3.4 The Specialist Advisors stated that the evidence from RCTs is limited, and that this procedure was one of a number of ablation techniques that uses different energy.
2.4.1 In the RCT, uterine perforation occurred during sounding before treatment in 0.5% (1/186) of patients, and there were three serious adverse events that occurred more than 15 days after the procedure (and within 12 months). These were severe abdominal cramping (two patients) and severe vaginal bleeding (one patient). Other adverse events reported at up to 12 months' follow-up included: abdominal or pelvic pain/cramping in 14% (26/186) of patients; uterine cramping in 4% (7/186); vaginal infection in 4% (7/186); hot flushes in 2% (3/186); urinary tract infection in 1% (2/186); and nausea and vomiting in 0.5% (1/186).
2.4.2 In the prospective case series of 67 women, adverse events reported immediately after the procedure included urinary frequency or urgency (100%), moderate pelvic pain, dysuria and vaginal discharge (the numbers of patients were not well reported). Other less commonly reported adverse events were prolonged tiredness and perimenopausal symptoms.
2.4.3 The adverse events reported in the US Food and Drug Administration Center for Devices and Radiological Health MAUDE database included excessive bleeding, uterine perforation bowel injury and stenosis of the cervix. For more details, refer to the Sources of evidence.
2.4.4 The Specialist Advisors stated that the procedure appears to be safe, but there are no data available on the incidence of major complications. The theoretical adverse events include thermal injury to the cervix and vagina. Anecdotal adverse events include persistent discharge and endometritis.