Phase I prehysterectomy studies of the transcervical administration of quinacrine pellets.

To determine the safety of transcervical administration of quinacrine pellets as a method of voluntary female sterilization, three noncomparative Phase I clinical trials of the administration of 250 mg quinacrine were carried out in 21 women who were scheduled to undergo hysterectomy 24 h or one month later. Detailed results are presented for one of the trials using 10-min pellets. Six of 10 women had minor transitory complaints during the postinsertion 24-h follow-up period. Five women reported pelvic/abdominal cramping, one experienced headache, and one experienced dizziness. Blood chemistry values were not adversely influenced by the quinacrine. The average plasma level of quinacrine peaked at 3 h, 36.1 ng/ml, slightly lower than the value observed 4 h after oral administration of 200 mg in a previous study. An average of 27% of the administered dose was recovered in tampons. Quinacrine was detected in the plasma of two women at the four/six-week visit. Selected results are presented from two other trials that were halted because of slow recruitment. The transcervical administration of 250 mg of 10-min quinacrine pellets was well tolerated. However, based on recent mutagenicity testing and meetings with regulatory officials, it appears unlikely that the use of quinacrine for nonsurgical sterilization could be approved in the United States or Europe.

Lamicel for induction of labor.

Lamicel is a synthetic osmotic cervical dilator currently used as a method of cervical dilation in first- and second-trimester pregnancy termination. It works by extracting fluid from the cervical tissue and softening the cervix. This study evaluated its effectiveness in nonelective medical induction of labor in high-risk patients. Forty inpatients who, for medical and obstetric reasons, required delivery within the next 24-48 hours were studied. Patients were evaluated to make certain that a 12- to 24-hour delay was safe for mother and child. The evening prior to the day of induction, a pelvic examination determined the Bishop score, and bacterial cultures were obtained from the endocervix. As many Lamicels as possible (usually one to three) were then placed in the endocervix without rupturing the membranes. The next morning the devices were removed, a repeat Bishop score obtained, amniotomy performed, internal monitors placed and oxytocin infusion initiated. Data were collected for preinsertion and postinsertion Bishop scores, induction-delivery times, duration of ruptured membranes, and cesarean and vaginal birth rates. Maternal and neonatal infectious morbidity was determined. A comparison group of patients with premature rupture of the membranes was selected. From data studied at our institution, patients were matched for parity and duration of labor (not significantly different from the Lamicel group). The study revealed that Lamicel can be an effective means of ripening the cervix for induction of labor.

Management of breech presentations in developing country hospitals.

PIP: This paper reports the results of an analysis of singleton breech presentations, alive at the onset of labor and with no congenital anomalies. There is no significant benefit from abdominal delivery for small or very small babies because developing country hospitals lack the neonatal care facilities to care for the low birth weight babies. For babies over 2500 grams, vaginally delivered babies are more than twice as likely to die before their mothers are discharged from the hospital. Parous women are more likely than are primipara to safely deliver breeches vaginally. In developing countries the possibility of maternal morbidity is at once greater and more serious because of fewer resources to provide adequate care. In deciding whether to deliver a breech abdominally or vaginally physicians should ask the following questions: 1) Are neonatal care facilities adequate for the small baby delivered alive? 2) What is the mother's parity and what are her future reproductive plans? 3) Will future deliveries occur at home or in a hospital? 4) Will she consider tubaligation at the time of cesarean section? 5) What is the hospital's record of maternal morbidity and mortality for cesarean sections? and 6) What is the physician's skill in delivering breeches vaginally and in performing cesarean sections?^ieng

The use of prostacyclin analogue-containing suture for the prevention of postoperative venous thrombosis in the rat.

The ability of prostacyclin analogue incorporated into a controlled-release suture to prevent postoperative venous thrombosis was investigated. Thirteen rats underwent bilateral transection and anastomosis of the common femoral vein. In each animal, polycaprolactone suture containing 0.25 micrograms/cm of the prostacyclin analogue Iloprost (Schering Ag, Berlin, West Germany) was used to perform the anastomosis on one vessel. Similar suture without prostacyclin analogue was used on the contralateral vessel, which served as a control. Functional patency and luminal surface morphology were assessed 24 hours postoperatively. All anastomoses performed using suture containing prostacyclin analogue were patent. Among controls, five anastomoses were patent and eight were occluded. This difference was highly significant (p less than 0.005). All anastomoses performed with prostacyclin analogue-containing suture exhibited a uniform absence of thrombosis. In contrast, eight control veins exhibited a dense, well-organized fibrinous clot that filled the entire lumen, effectively sealing off the vessel. These results suggest that the prostacyclin analogue released from the suture was highly effective in inhibiting thrombus formation without adversely affecting the vessel's ability to achieve hemostasis.

Delivery type and neonatal mortality among 10,749 breeches.

Data on 10,749 breech presentations were analyzed for the effect of delivery type on neonatal mortality. Most of the data are from developing countries, and most of the hospitals have higher mortality than is found in Europe or the United States. The simultaneous effect of type of hospital where the delivery occurred, type of breech, birthweight, and parity were examined. The benefit of cesarean delivery was greater for nulliparae than multiparae, greater for footlings than for frank or complete breeches, and greater for larger babies than smaller ones. This last finding probably reflects the quality of neonatal care in developing country hospitals rather than the value of cesarean section. Maternal mortality and morbidity was higher among women delivered abdominally than among those delivered vaginally.

Survey of obstetric forceps training in North America in 1981.

In April, 1983, a questionnaire was sent to all 144 United States and Canadian members of the Association of Professors of Gynecology and Obstetrics to survey residency training and current use of obstetric forceps in 1981. One hundred five programs (73%), responsible for at least 283,000 births in 1981, were subsequently analyzed. All training programs used outlet forceps and all programs but one used midforceps for delivery. Hospitals with high cesarean birth rates did not perform significantly fewer midforceps operations. Hospitals with high midforceps rates did not also have high outlet forceps rates nor did these high rates closely reflect the personal attitude to obstetric forceps of the director of the obstetric training program. Simpson's forceps were most commonly used for outlet forceps and occipitoanterior midforceps operations, whereas Kielland's forceps were selected by 76% of programs for rotational midcavity deliveries. Staff obstetricians were the primary instructors of forceps technique in the delivery room in only 50% of United States programs; all Canadian respondents reported the staff obstetrician as the principal educator in obstetric residency forceps training.

Postpartum insertion of modified intrauterine devices.

The immediate postpartum insertion of standard intrauterine devices (IUDs) and those specially modified for postpartum use was evaluated in a multicenter clinical trial. The immediate postpartum insertion of IUDs was not associated with any increased risk of perforation or infection, although expulsion rates were higher than with interval insertions. The expulsion rate varied widely between centers using similar devices, suggesting that training in insertion is essential. Postpartum IUD insertions can be a practical contraceptive option for patients and providers of medical services.

PIP: The postpartum insertion of IUDs, especially in the case of institutional deliveries, has a number of advantages, including ease of insertion, availability of skilled personnel, appropriate facilities, and convenience for the mother. Immediate postpartum insertion of IUDs is not associated with increased risk of perforation or pelvic inflammatory disease (PID), although expulsion rates are higher than with interval insertions. In studies by Family Health International (FHI), expulsion rates varied widely between centers using similar devices. Expulsion rates ranged from 6-37/100 women at 6 months after insertion. This finding suggests that insertion may be as important a factor in influencing expulsion as the configuration of the device. FHI has developed modified IUDs with added suture material to project into the endometrium and reduce expulsion. After insertion the suture projections become soft and pliable and biodegrade completely within 6 weeks. Standard IUDs used for modification were the TCu and Lippes Loop. Adequate training and supervision of delivery room staff in insertion of IUDs is necessary. Midwives can betrained to insert the IUD after parturition through demonstrations and followup monitoring. Timing of IUD insertion is very important; FHI data show a significantly higher (p0.05) expulsion rate associated with insertions performed within the period of 10 minutes to 36 hours as compared to the immediate postpartum period (within 10 minutes). The use of postpartum IUDs raises questions of how much overlap there will be with the natural suppression of ovulation, especially in breastfeeding women, and whether the altered physiology of the reproductive tract interacts with the method. The inability to predict for individual women when ovulation will return, particularly among those who are breastfeeding, combined with inconvenience and sometimes impossibility of returning to a medical facility for insertion make the compromise of immediate postpartum insertion demographically effective and reasonable in many circumstances.

[Post-partum and post-abortal use of IUDs (author's transl)]. / Le D.I.U. dans le post-partum et le post-abortum.

PIP: The search for an IUD that could be safely inserted in the immediate postpartum period and retained as long as desired led the Population Council to undertake a 13-center study of Lippes loop insertion during the 1st 10 postpartum days. The expulsion rate of 20.5% in the 1st 3 months following insertion was considered too high, despite apparently lower risks of perforation and infection. In 1975 the International Fertility Research Program (IFRP) began a program to modify existing IUDs for immediate postpartum and postabortal insertion. Several approaches were explored using biodegradable materials to avoid expulsion, and a modified Lippes loop with catgut sutures gave good results. A case study undertaken by the IFRP attempted to evaluate too many factors with too little attention to the qualifications of participating physicians, resulting in highly variable experiences in different centers. A program recently initiated in 10 collaborating centers in Turkey promises to yield interesting results; preliminary indications are that success rates vary between institutions and depend partly on the enthusiasm of the program director. 1 Turkish center solved the difficult problem of follow-up by adding a clinic where the newborns received check-ups. In 1 month, with 100% follow-up, over 100 IUDs were inserted and only 1 of the last 50 was expelled. Many IUDs inserted postpartum are expelled because they are not placed sufficiently deeply in the uterine cavity. The IFRP believes that with appropriate training of personnel and a better tool for insertion, a high rate of retention can be achieved. Within 6 months the IFRP expects to begin clinical testing of a 2nd generation postpartum IUD with improved sutures. Despite variable success in the past, development of a satisfactory postpartum IUD would be a valuable addition to many national family planning programs.^ieng

The introduction of postpartum intrauterine devices in the People's Republic of China.

In China, which has a commitment to family planning and, in particular, to the one-child family, a postpartum IUD should be widely accepted and could have significant impact on the Chinese family planning program. This report presents the introduction of the Delta T and Delta Loop devices, with 200 immediate postpartum insertions. Fifty-two deliveries were by cesarean section. The 6-month expulsion rates were 13.3 and 17.2 for the Delta T and Delta Loop, respectively. There was one pregnancy reported. Analysis suggests that the two devices are suitable for use in the postpartum period for Chinese women.

PIP: Since 1956, China has had an official policy favoring birth control, and in 1962, it became "a national policy of highest priority". The government began encouraging 3 reproductive norms: later marriage, with the legal age for marriage now being 22 for males and 20 for females; longer spacing between births, with at least 4-year interval recommended between births; and fewer children, meaning 2 children per family in 1977. Since then, a new family planning campaign has been introduced that calls for elimination of all 3rd and higher order births by 1982 in some areas and for encouraging the 1-child family as much as possible. Available contraceptives that can be provided by paramedics, which are highly effective, and which can be used in the immediate postpartum period while the woman is still under the care of birth attendants are recommended. The postpartum Loop and postpartum T intrauterine devices with biodegradable chromic sutures have been developed and named the Delta Loop and the Delta T. They are both modifications that involve the addition of chromic suture extensions to standard Lippes Loop D and Copper T 220C devices, respectively. From December 1980 through March 1981, 108 Delta T and 92 Delta Loop devices were inserted in women within 10 minutes following delivery of the placenta. 52 deliveries were by cesarean section. The 6 month expulsion rates were 13.3 and 17.2 for the Delta T and Delta Loop, respectively. There was 1 pregnancy reported. In a society such as the People's Republic of China where strong emphasis is placed on family planning and, specifically, on the 1-child family, the availability of a safe and highly effective contraceptive during the puerperium is ideal. Since the IUD itself has been proven effective and acceptable in China, a postpartum device could add another dimension to family planning, especially for couples not ready for permanent contraception.

Comparison of the Lippes Loop D and tapered Lippes Loop D intrauterine devices.

The tapered Lippes Loop D (LLD) is compared to the standard LLD to evaluate efficacy and termination events. The tapered device was designed with the intention of lowering the expulsion rate below the rate for women with standard Lippes Loops. The two devices were randomly assigned to 989 women in two studies. Expulsion rates for the tapered device were lower at six months (p less than 0.10) and at 12 months (p less than 0.05). When the women were divided into groups by uterine measurement, the differences continued to be significant for women with larger uteri but not for those with smaller uteri. Comparison of other pertinent event rates showed no significant differences. Analysis of the data indicates that the tapered LLD represents an improvement in expulsion rates over the standard LLD.

Chemical sterilization with an IUD.

Zipper has more than adequately demonstrated that quinacrine, when placed in the uterine cavity, has a sclerosing effect on the tubal ostia, resulting in chemical sterilization of the fallopian tubes. His technique involves the use of 3 monthly instillations of 250 mg of pellets into the uterine cavity. With the hope of reducing the total dosage and making it a 1-insertion technique, quinacrine has been mixed with polyethylene oxide and place on the arms of various IUDs. It is hoped that the material is directed at the tubal ostia. Studies to date have occurred in women awaiting hysterectomy with careful pathologic examination of the intramural portion of the tube. The results thus far are most encouraging and once the best vector is identified, it is hoped that this will become an acceptable means of female sterilization.

[Chemical Sterilization with an I.U.D. (Author's transl)]. / Sterilization chimique par D.I.U.

PIP: The idea of utilizing an IUD as a vector to introduce sclerotic agents in the tubes, is not a new one, and experiments have been, and are being, carried out in several countries. The author of this study has experimented with a Copper-T-Device delivering quinacrine hydrochloride to the tubal ostia in women who had to undergo hysterectomy. Examination of the specimens showed tubal occlusion in 50% of cases. It seems that other researchers have obtained a 75% of success thanks to an extremely rigorous insertion of the device, since it appears obvious that there is a correlation between the intrauterine position of the device and its pathological consequences.^ieng

Endometriosis and the development of tuboperitoneal fistulas after tubal ligation.

The present study details gross and histologic findings of 79 previously ligated fallopian tubes from 3 groups of patients. Of 20 oviducts removed after documented sterilization failure (group I), 6 revealed a process compatible with endometriosis. Four of nine previously ligated fallopian tubes removed at the Johns Hopkins Hospital (group II) were successfully injected with India ink. In two patients histologic examination demonstrated the India ink in epithelium-lined spaces that lay beyond the muscle of the tubal wall extending from the tubal lumen to the serosal surface. Fifty oviducts were studied in twenty-five patients requesting reversal of their sterilizations (group III). A higher percentage of fistulas was demonstrated in patients with less than 4 cm of remaining proximal tubal segment. Furthermore, most of these fistulas were demonstrated in patients for whom 3 years had elapsed since the original sterilization procedure. Patients sterilzed by laparoscopic cautery methods were observed to have a higher percentage of fistula formation and histologic documentation of endometriosis at the sterilization site as compared with patients sterilized by other methods. Our observations suggest that ligation of the oviduct within 4 cm of the uterine cornu may predispose to the development of endometriosis and subsequent fistula formation in the tip of the ligated oviduct.

PIP: Gross and histological findings of 79 previously removed fallopian tubes from 3 groups of patients are reported. Of 20 tubes removed after documented sterilization failure (Group 1), 6 showed endometriosis. 4 of 9 previously ligated tubes (Group 2), were injected with ink; 2 patients showed ink in epithelium-lined spaces beyond the muscle of the tubal wall from the tubal lumen to the serosal surface. Group 3 was 50 oviducts from 25 patients requesting reversal of sterilizations. In this group a higher percentage of fistulas was demonstrated in those with less than 4 cm of tube remaining in the proximal segment. Also, most of these fistulas were in patients 3 years or more away from the original procedure. Laparoscopic cautery sterilizations had higher percentages of fistula formation and endometriosis at sterilization site than sterilizations by other methods. Therefore, ligation of the fallopian tube within 4 cm of the uterine cornu may predispose development of endometriosis and subsequent fistula formation at the tip of the ligated tube.

Technical failures in tubal ring sterilization: Incidence, perceived reasons, outcome, and risk factors.

Six centers participated in comparative studies of female sterilization conducted by the international Fertility Research Program. The incidence of technical failures (or failed attempts) was compared between patients sterilized with the tubal ring and those sterilized with other tubal occlusion techniques. The tubal ring was associated with a higher failure rate than electrocoagulation, the Rocket clip, or the modified Pomeroy technique. Of 1,035 tubal ring sterilizations, there were 38 technical failures. Reasons given by the operators for the failures, by frequency of occurrence, were surgical complications, conditions preexisting in the patients, and problems with the instruments. Most of these failures were remedied by changing to other techniques. In two patients, the procedure was completed by changing the approach from laparoscopy to laparotomy. In five others, sterilization was not completed. Case-control analysis was performed and three risk factors were delineated: obesity, prior use of an intrauterine contraceptive device and previous abdominal operations.

PIP: 6 centers participated in comparative studies of female sterilization conducted by the International Fertility Research Program. The incidence of technical failures (or failed attempts) was compared between patients sterilized with the tubal ring and those sterilized with other tubal occlusion techniques. The tubal ring was associated with a higher failure rate than electrocoagulation, the rocket clip, or the modified Pomeroy method. Of 1035 tubal ring sterilizations there were 38 technical failures. Reasons given by the operators for failures by frequency of occurrence were surgical complications, conditions preexisting in the patients, and problems with the instruments. Most of these failures were remedied by changing to other techniques. In 2 patients, the procedure was completed by changing the approach from laparoscopy to laparotomy. In 5 others, sterilization was not completed. Case-control analysis was performed and 3 risk factors were delineated--obesity, prior use of an IUD, and previous abdominal surgery.

Laparoscopic sterilization with room air insufflation: preliminary report.

Laparoscopic sterilizations can be safely performed using room air insufflation. In a series of 400 procedures, the rates of surgical complications were comparable to other laparoscopy studies in which high-pressure gas was used. The purported problems associated with room air insufflation were not encountered in this study.

PIP: This paper reexamines the use of room air as the insufflating medium for voluntary sterilizations. 400 sterilization procedures were performed at the Centro Medico in El Salvador. The 1st 100 sterilizations utilized a standard laparoscopy technique that familiarized the operating physician with the laprocator. The next 300 sterilizations utilized Hasson's open laparoscopy technique using the Hasson trocar and blunt cannula. In all the procedures, pneumoperitoneum by room air was used for insufflation. Air insufflation was achieved using the KLI insufflator which can deliver either gas under pressure or air with a pneumatic bulb. No surgical recovery period or follow up complications were observed in the standard laparoscopy series. Of the 300 open laparoscopy procedures, 1 case (0.3%) of mesosalpingial injury without bleeding was recorded as a surgical complication. Follow-up complications were 2 cases (0.7%) of urinary tract infections and 2 cases (0.7%) of incision inflammation that required medical treatment with only aspirin or penicillin. Reported sites of pain during standard laparoscopic procedures were pelvic (5%) and shoulders (2%). Benefits of use of room-air insufflation are universal availability, low cost, simplification of procedure, reduction of cost of backup equipment and reduction of performance time. The reported disadvantages of room air insufflation--pain, air embolism, infection or death--did not occur in this series.

Menstrual pattern changes in laparoscopic sterilization patients whose last pregnancy was terminated by therapeutic abortion. A two-year follow-up study.

Women were used as their own controls in the comparison of presterilization and poststerilization menstrual patterns. Five parameters were studied: regularity of cycle length, duration and amount of flow and incidence of dysmenorrhea and intermenstrual bleeding. Three parameters in the electrocoagulation group (regularity of cycle length and duration and amount of flow) and one parameter in the tubal ring group(duration of flow) showed significant changes after sterilization. However, by controlling for the effect of previous contraceptive methods used, no significant menstrual pattern changes following sterilization were discerned in either technique group.

PIP: Between 1973 and 1975, 2501 women were sterilized by laparoscopy at the Yonsei University College of Medicine in Seoul, Korea. The women were used as their own controls in a follow-up study of the changes in menstrual patterns following sterilization. Tables present the results of the study. In the electrocoagulation group, twice as many patients changed from regular to irregular cycles than the other way; there was no such difference among the tubal occlusion group. More patients in both groups experienced a decline in menstrual flow. The aging of the patients and the fact that some had had therapeutic abortions prior to or concurrent with the sterilization procedure did not have any effect on the observed changes in menstrual cycles. Changes in menstrual cycle length, duration, and amount seemed to be associated with the type of contraceptive used previously. Controlling for prior contraceptive usage caused the observed differences in menstrual cycles to disappear.

[Improving IUD performance with biodegradable materials (author's transl)]. / Efficacite des D.I.U. accrue au moyen de matieres biodegradables.

PIP: A discussion of factors involved in developing IUDs for use in developing countries is presented. Postpartum or postabortion insertion of IUDs has several advantages: insertion is easier at this time; a return visit is not necessary; and the motivation to use contraceptives, the IUD in particular, is greater at this time. The rate of expulsions, side effects, and complications is, however, found to be considerably greater if the insertions are performed after childbirth or abortion. To alleviate this problem, addition of biodegradable materials is suggested as a possibility for improving IUD efficiency and retention. In modifying IUDs, the materials must be biocompatible; sufficiently absorbable in a predictable manner; be able to be sterilized; be able to be shaped as necessary, yet be frm enough to resist wear; and should be inexpensive. Modifie Lippes loop devices with extensions of collagens or polylactic acid-gel were unsuccessful because of size and difficulty of insertion. More successful are Lippes loop or Copper-T devices with chronic catgut sutures to help hold the IUD in palce. Experiments were performed unsuccessfully to determine if biodegradable matrices releasing substances such as Transylol could reduce bleeding, pain, and other IUD side effects. A non-biodegradable system of ethyl vinyl acetate releasing medications has proven acceptable so far, but more testing is needed.^ieng

Modification of the CuT 220C for immediate postpartum use.

PIP: Postpartum insertion of IUDs has an unacceptably high expulsion rate. The International Fertility Research Program (IFRP) modified the Lippes Loop D and Copper T 220C with chronic suture extensions (Ethicon, No 2) for postpartum insertion. These biodegradable extensions or projections are added to the IUD to hold them in place during the involution period. Preliminary data shows that such modified devices have an expulsion rate of 5.3 + or - 1.3 per 100 women at 6 months. A clinical trial of 247 hand insertions performed in the immediate postpartum period (within 10 minutes after delivery of placenta) in Chile and in the Philippines revealed an expulsion rate of 4.2 + or - 1.3 at 3 months, and 6.5 + or - 1.6 at 6 months after insertion, rates similar to those of the sutured loop (3.1 + or - 1.0 and 5.3 + or - 1.3, respectively). At 6 months and 1290 women-months of use, continuation rate was 91.7%. Preliminary data also suggest a success rate for the sutured Copper T 22OC similar to that of the sutured Lippes Loop D. These data also imply that modification of any standard device for immediate postpartum insertion for increased effectiveness can be achieved if done in a similar way.^ieng