Thermoregulated radiofrequency endometrial ablation.

OBJECTIVE: To test the hypothesis that treating dysfunctional uterine bleeding by automated application of electrothermal energy to the uterine cavity, with precise regional control, might yield results equivalent to those reported for hysteroscopically directed laser and electrosurgical endometrial ablations. MATERIALS AND METHODS: Patients with life style compromising menorrhagia, referred to six gynecologic surgical centers for hysterectomy or endometrial ablation, were admitted to the study if they had normal cervical cytology, a benign endometrial biopsy, no defined cause for their bleeding, and consented to participate in the evaluation of a newly developed Vesta DUB Treatment System. The device consists of a silicone-inflatable electrode carrier to be inserted into the uterine cavity and a controller to monitor and distribute current from a matched electrosurgical generator. Treatment involved a 3-minute or shorter warm-up period and a 4-minute treatment phase. RESULTS: Three- to 24-month follow-up data were available for 187 patients, with a mean follow-up of 14.8 months. The amenorrhea rate was 38%. Bleeding was reduced in 95% of patients. Actuarially, 88 +/- 3% of patients should expect to be free of menorrhagia, dissatisfaction, or need for a second procedure out to 24 months. CONCLUSIONS: The unique regional feed-back control offered by this system causes thorough, evenly distributed, thermal destruction 4-5 mm into the myometrium that reduces bleeding with durability equivalent to published reports of hysteroscopic endometrial ablation.

The GyneFix implant systems for interval, postabortal and postpartum contraception: a significant advance in long-term reversible contraception. International Study Group on Intrauterine Drug Delivery.

Intrauterine contraception has a number of important advantages over other forms of contraception and remains, therefore, an important method of birth control. However, side-effects and other drawbacks have reduced its overall acceptance. Also misconceptions and lack of updated scientific knowledge among the potential users and providers are major obstacles to the widespread use of intrauterine contraception. Ideally, an intrauterine device (IUD) should prevent pregnancy effectively, be well tolerated, not become displaced or expelled over time, cause a minimum of side-effects, be long-lasting, have a strictly local effect, and be easy to insert and remove. A group at the University of Ghent, Belgium, the International Study Group on Intrauterine Drug Delivery, has developed, since 1985, a totally new concept in order to improve current intrauterine contraceptive efficacy and enhance tolerance, by creating a harmonious relationship between the uterine cavity and the contraceptive 'foreign body'. The new concept (GyneFix) consists of a non-biodegradable suture thread made of surgical 00 monofilament polypropylene on which six copper tubes are threaded, providing a total surface area of 330 mm2. The upper and lower tubes are crimped onto the thread to keep the tubes in place. The upper extremity of the thread is provided with a knot which serves as an anchor. The knot is implanted in the myometrium of the uterine fundus with a specially designed insertion instrument, thereby permanently securing the device in the uterine cavity. Since the initial clinical investigations, over 10,000 woman years of experience and up to 10 years' follow-up in international multicenter, non-comparative and comparative clinical trials have been collected. The clinical material also included a large number of nulligravid and nulliparous women. Due to the design characteristics of the GyneFix and its anchoring in the uterine fundus, an optimal tolerance and almost complete absence of expulsion were obtained. The constant release of copper ions in the upper part of the uterine cavity results in the high effectiveness of the anchored device. The effectiveness is higher than in the high-load conventional copper IUDs which have a risk of becoming displaced, partially or totally expelled in 10% or more (nulliparous women), resulting in a significant number of accidental pregnancies. The absence of frame and, as a consequence, its flexibility, explain the low incidence of side-effects and the very low incidence of complications, such as pelvic inflammatory disease and ectopic pregnancies. This new concept could be a major step forward in the acceptance of intrauterine contraception worldwide and increase its popularity. This article reviews the experience with the new concept for interval, postabortal and postpartum contraception.

[Intrauterine copper contraceptive implants]. / Implant intra-utérin contraceptif au cuivre (ICIU).

GyneFix, conceived in 1985, was developed to minimize three major problems frequently associated with discontinuation of IUD use: expulsion, bleeding and pain. Since the initial clinical investigations, over 10,000 women years of experience and up to 8 years of follow-up in international, multicenter, non-comparative and comparative clinical trials, including a large proportion of nulligravid/nulliparous women, have been collected. The following conclusions were reached: 1. The unique design characteristics of GyneFix (frameless, flexible and fixed to the fundus of the uterus) have resulted in optimal tolerance and almost complete absence of expulsion. The result is enhanced effectiveness (comparable to OCs and male/female sterilization) and a high rate of continued use. GyneFix reduces the IUD-failure rate to a minimum and is, therefore, a welcome reversible alternative to OCs and female surgical contraception. 2. Frameless and flexibility explain the absence of side-effects and adverse events caused by dimensional incompatibility between the frame of conventional IUDs and the uterine cavity and may also explain the absence of PID and ectopic pregnancies in any of the clinical studies. 3. Insertion of GyneFix, with or without local anaesthesia, is easily accomplished in the office of a few minutes. Removal is easy, quick and painless. 4. GyneFix is an equally effective and well accepted method fro nulliparous women.

Endometrial ablation using a distensible multielectrode balloon.

The VestaBlate system uses a multielectrode intrauterine balloon as a device to create effective and safe endometrial ablation (EA). The surface of the distensible balloon is impregnated with thermistors and thin, platelike electrodes. It is designed to deliver low-power electroenergy to the endometrium. Unlike the resectoscope techniques that require nonelectrolytic fluids for uterine distention, moving electrodes at high power outputs, and other variables that are operator dependent, the VestaBlate is computer controlled using a standard type electrosurgical generator. A respiratory enzyme stain, nitroblue tetrazoleum, was used to determine the extent and depth of tissue necrosis to a myometrial depth of 2 to 4 mm with uniform destruction of tissue with power setting at 45 W for a 4-minute application of energy. Sixty-nine patients have been treated, with 45 followed for at least 3 to 9 months. The amenorrhea rate is 40%; the oligomenorhea-hypomenorrhea rate is 49%.

A randomized comparative study of the TCu380A and Cu-Safe 300 IUDs.

The Cu-Safe 300 is one of the latest additions to the array of available IUDs. It was specifically designed to decrease unwanted side-effects (e.g. bleeding, pain and expulsion) while providing simplicity of insertion, ease of removal and fair contraceptive protection. For comparison, the TCu380A was chosen. Both types were inserted at random in 600 recipients by a group of independent physicians with a long standing experience in intrauterine contraception. Life table analysis was used for comparison over a period of three years. The Cu-Safe 300 produced a slightly but not statistically significant higher pregnancy rate and more expulsions. Removals for bleeding and pain, however, were significantly less frequent. All inserting physicians agreed that insertion and removal of this new device was remarkably easy.

The frameless GyneFix intrauterine implant: a major improvement in efficacy, expulsion and tolerance.

The CuFix (GyneFix), conceived in 1985, was developed to minimize three major problems frequently associated with discontinuation of IUD use: expulsion, bleeding and pain. Since the initial clinical investigations, over 10,000 woman years of experience and up to 8 years of follow-up in international multicenter, non-comparative and comparative clinical trials, including a large proportion of nulligravid/nulliparous women, have been collected. Based on new clinical information about the GyneFix from a long-term multicenter clinical trial, conducted in young nulligravid/nulliparous and parous women, the importance of this new contraceptive is discussed. The following conclusions were reached: The unique design characteristics of the GyneFix (frameless, flexible and fixed to the fundus of the uterus) have resulted in optimal tolerance and almost complete absence of expulsion. The result is enhanced effectiveness (comparable to OCs and male/female sterilization) and a high rate of continued use. The GyneFix reduces the IUD failure rate to a minimum and is, therefore, a welcome reversible alternative to OCs and female surgical contraception. Framelessness and flexibility explain the absence of side-effects and adverse events caused by dimensional incompatibility between the frame of conventional IUDs and the uterine cavity and may also explain the absence of PID and ectopic pregnancies in any of the clinical studies. The GyneFix is a promising new, highly effective and safe, contraceptive option for parous women and an equally effective and well-accepted method for nulliparous women.

IUD expulsion solved with implant technology.

In an attempt to minimize the problem of IUD expulsion, implantation technology has been developed and tested. The trials have extended from 1985 until the present time for interval as well as for immediate postabortal and post-placental insertion and fixation of the CuFix IUD (Gyne-Fix). The present article reports on an ongoing study with GyneFix interval insertion, with an improved inserter, in 820 women, observed up to 3 years, of whom 213 (25.9%) are nulligravid/nulliparous. The cumulative expulsion rate is 0.6 per 100 women-years at 3 years and is not significantly higher in the nulligravid/nulliparous group. The cumulative pregnancy rate is 0.6 and the cumulative removal rate for medical reasons 3.2 at 3 years. The total experience in this multicenter study covers approximately 14,000 woman-months. It is concluded that the design characteristics of the GyneFix (fixed, frameless, and flexible) explain the low expulsion, high efficacy and high acceptability rates. The implantation technology is very effective and the improved inserter allows easy insertion and optimal anchoring.

Fertility after hysteroscopic myomectomy.

The available data concerning hysteroscopic myomectomy for submucous myomas has been reviewed with the aim of evaluating the safety and efficacy of this technique in infertile women who wish to preserve or to enhance their fertility potential. A total of 134 infertile patients undergoing hysteroscopic myomectomy by resectoscope or by Nd: YAG laser or by scissors have been collectively recorded. Of these, 79 (58.9%) patients conceived. This clinical outcome is similar to that occurring after laparotomic submucous myomectomy. Moreover, the hysteroscopic approach has several advantages over its abdominal counterpart, such as reduction of length of time of hospitalization, less morbidity and no hysterotomy. The operative risk of hysteroscopic myomectomy is < 3%. Uterine perforation, distension system hazard, infection and haemorrhage are the commonest complications. Hysteroscopic myomectomy is a safe, effective and relatively simple surgical procedure for the restoration of fertility.

Immediate postplacental insertion and fixation of the CuFix postpartum implant system.

Since promising results were obtained with the CuFix interval implant system in international clinical trials conducted worldwide, a modification of the device adapting it for immediate postplacental insertion and fixation (IPPIF) seemed a logical approach to solve the expulsion problem of IUDs inserted at that particular time. Seventy-three insertions were performed at three university centers, during 1990 and 1991, both by skilled and unskilled investigators. The results of this multicenter study show the excellent retainability of the modified IUD supporting the validity of the anchoring principle. The insertion procedure is easy, requiring minimal training, and the insertion technique appeared to be safe.

PIP: Physicians inserted the CuFix postpartum (CuFixPP) implant system, an IUD, to a depth of 1.3 cm in the fundal myometrium in 73 healthy women soon after vaginal delivery (10-30 minutes) at either the University Hospital in Gent, Belgium; the University Medical School in Debrecen, Hungary; or Alexandra Hospital of the University of Athens in Greece. Since previous international clinical trials showed unacceptably high rates of expulsion of CuFixPP, researchers conducted this trial to test the IUD after having it modified for immediate postplacental insertion and fixation. None of the physicians had received training in the insertion procedure of this experimental IUD. The cumulative expulsion rate at 12 and 18 months was 3.1. The cumulative pregnancy rate at 12 and 18 months stood at 1.5. The sole reasons for removal at 12 and 18 months were bleeding/pain and planned pregnancy (7.4 at 12 and months and 10.8 at 18 months; 9 at 12 months and 12.2 at 18 months, respectively). Physicians experienced difficulty removing the IUD in 4 cases. The removals did not cause noticeable bleeding. No complications occurred. These findings revealed that, with further modifications, the CuFixPP IUD holds considerable promise as a simple and effective method of postpartum contraception, which can easily be inserted by nurses or midwives, especially in developing countries.

Potency and selectivity of the aromatase inhibitor R 76,713. A study in human ovarian, adipose stromal, testicular and adrenal cells.

The effects of R 76,713 on steroidogenesis were studied in primary cultures of four different human cell types, i.e. ovarian granulosa cells, adipose stromal cells, testicular cells and adrenal cells. In human granulosa cells aromatization of [1 beta, 2 beta-3H]androstenedione (as measured by the release of tritiated water) showed a Km (Michaelis constant) of 78 nM. R 76,713 competitively inhibited aromatization with a Ki (dissociation constant of the enzyme-inhibitor complex) of 1.6 nM. In human adipose stromal cells aromatization was measured by following the conversion of androstenedione to estrone and 17 beta-estradiol. In this system a Km for aromatization of androstenedione of 10.8 nM was found. R 76,713 again showed competitive kinetics with a Ki-value of 0.14 nM. In human testicular cells the synthesis of the androgens testosterone, androstenedione and dehydroepiandrosterone was only inhibited by drug concentrations exceeding 10(-6) M. At 10(-5) M of R 76,713, steroid concentrations were lowered to 56, 64 and 81% of the control for testosterone, androstenedione and dehydroepiandrosterone respectively. Concomitantly, a slight increase in the levels of pregnenolone (138% of the control) and progesterone (133% of the control) was seen. In human adrenal cells the synthesis of cortisol and aldosterone was slightly affected by R 76,713 also at concentrations exceeding 10(-6) M. At 10(-5) M of R 76,713 the concentrations of cortisol and aldosterone were lowered to respectively 59 and 51% of the control. At the same drug concentration the precursors 11-deoxycortisol and 11-deoxycorticosterone rose to 189 and 147% of the control. These results show that in primary cultures of human cells, R 76,713 is a very potent aromatase inhibitor with a selectivity of at least 1000-fold compared to other steps in steroidogenesis.

Long-term experience with Multiload intrauterine devices.

This paper reports the joint experience of three investigators who used three types of the Multiload (ML) IUD (MLCu250 Short, MLCu250 Standard, and MLCu375) in 1987 consecutive insertions during which an experience of 56,005 woman-months of use was accumulated. The material was analyzed using the life-table method and complemented with a case by case investigation, the main purpose of the study being the specific analysis of IUD-related complications. The authors also evaluated return of fertility whenever a device was removed because of wish of pregnancy. Results indicate that serious IUD-related complications were rare, continuation rate high, and reversibility of fertility unaffected by the device.

[The levonorgestrel intrauterine device]. / Das Levonorgestrel-Intrauterinpessar.

The levonorgestrel IUD offers a valuable improvement for women, who develop menorrhagia with conventional IUDs. However, since the levonorgestrel Nova-T induces amenorrhea and spotting in a substantial proportion of the patients, it is advisable, before insertion, to evaluate the acceptor's reaction to the "new" bleeding pattern induced by the steroid IUD.

The Copper-Fix (Cu-Fix): a new concept in IUD technology.

The Copper-Fix (Cu-Fix) is a thread-type copper-bearing device designed to overcome the most common IUD-related problems: bleeding and pain. Two distinctive features--virtual absence of a frame and provision of an anchoring system--make this new intrauterine device the first radical departure from current IUD technology. The Cu-Fix 390 was inserted at intervals in 382 women, and 4851 woman-months of experience had been accumulated at 18 months. The device was exceedingly well retained by the uterus (expulsion rate 0.6 at 18 months) and the removal rate for bleeding/pain was low (3.1 at 18 months). Serious complications did not occur; the pregnancy rate amounted to 0.3 at 18 months, with a continuation rate of 87.6%, which includes an 8.1% removal rate for pregnancy wish. Cardinal event rates were not influenced by the age or gravidity status of the recipient.

Is hysteroscopy of value in the investigation of female infertility?

A prospective multicentre study was designed to ascertain the value of hysteroscopy in the evaluation of female infertility. The study comprises 619 CO2 hysteroscopies in women complaining of infertility. Four hundred and ninety nine examinations (80%) were performed without anaesthesia or cervical dilatation. Twenty eight cases of malformation were diagnosed. Adhesions were found in 68 patients (11%), polypi in 56 (9.1%) and submucous fibroids in 51 (8.2%). Endometrial hyperplasia was diagnosed by hysteroscopy in 67 patients, but there was only 42% histological correlation. Examination of the tubal ostia by hysteroscopy revealed 26 patients (4%) with unilateral tubocornual polyps and one with bilateral polyps. The correlation with hysterosalpingography (HSG) in 185 patients was poor. In 20% where the HSG was reported as normal there were hysteroscopically demonstrable lesions whereas there were false positive findings at HSG in 35% of cases. Hysteroscopy is the only technique which provides an accurate clinical evaluation of the uterine cavity although it does not provide significant information about the cervical canal or fallopian tubes.

Estradiol medicated IUDs: release and influence on menstruation pattern.

In a double blind trial of 90 women with three types of IUD (MLCu250; MLCu250 + 0.3 mg estradiol releasing about 1 microgram per day; and MLCu250 + 1.0 mg estradiol releasing about 3 micrograms per day) no difference in intensity or duration of bleeding was found.

The Ombrelle-380 IUD: a pilot study.

The initial results of a pilot trial (314 insertions and 3784 woman-months of experience at 18 months) suggest the low expulsion rate (0.0) and high clinical effectiveness (pregnancy rate 0.0) of the Ombrelle-380, a new high-load copper-releasing IUD of French origin.

Immediate postpartum insertion: performance of the Nova-T-PP and randomized comparison with the Nova-T.

Clinical evaluation of the Postpartum Nova-T or Nova-T-PP (a Nova-T IUD adapted for postpartum insertion) was based on 412 insertions and showed that this model--besides being effective and safe--had a low expulsion rate (7.2% at 1 year). To prove that the Nova-T-PP's low expulsion rate is indeed the result of its special design, a randomized trial was conducted to compare the Nova-T-PP with the parent model (Nova-T) when inserted within 10 minutes of delivery of the placenta. The result of this study (408 insertions, 203 of them Nova-T) indicate that there is no significant difference in expulsion rate between the two IUD models, suggesting that the addition of two extra arms to the original Nova-T model does not improve the retention of the adapted IUD model.

The Dimélys IUD.

The Dimélys is a new lily-shaped copper-bearing IUD of French origin of which the first clinical results are reported here. This device was inserted at interval in 348 women and 8975 woman-months of experience were accumulated at 3 years. Though only moderately effective (pregnancy rates 2.8 and 5.7 at 1 and 3 years, respectively) the Dimélys is well retained by the uterus (expulsion rates 1.5 and 2.5 at 1 and 3 years, respectively). Clinical efficacy was found to be influenced by the recipient's age, and expulsion rates were significantly higher when inserted by unskilled operators.