The safety and effectiveness of a new hysteroscopic method for permanent birth control: results of the first Essure pbc clinical study.

BACKGROUND: Current methods of female surgical sterilisation require incisional surgery, general anaesthesia and a prolonged recovery time. We studied the safety and effectiveness of Essure pbc, a minimally invasive, transcervically placed micro-insert that occludes the Fallopian tubes, resulting in permanent female contraception. Device under study: The Essure pbc implant is a dynamically expanding micro-insert which is placed in the proximal section of the Fallopian tube using a modified minimal access technology for cannulating the tube. STUDY POPULATION: Women aged 21-43 seeking permanent birth control. METHODOLOGY: Essure pbc micro-inserts were inserted into the proximal portion of the Fallopian tubes under hysteroscopic visualisation with intravenous sedation or paracervical block. RESULTS: Bilateral device placement was achieved in 111 of 130 (85%) women who underwent device placement attempts. Women found the device placement procedure to be highly acceptable. Of women wearing the device for up to two years rate, 97% rated it to be very good to excellent. There have been no pregnancies reported in 1894 woman-months of effectiveness. Adverse events preventing women from relying on Essure pbc were < 5%. DISCUSSION: This first clinical trial showed the Essure pbc method of permanent contraception to be safe and highly acceptable to women. Experience and improvements to the delivery system should increase overall micro-insert placement rates. CONCLUSION: The Essure pbc method of permanent contraception is an exciting alternative to vasectomy or laparoscopic sterilisation that does not require general anaesthesia or incisions.

New methods for transcervical cannulation of the fallopian tube.

Technological advances have led to major improvements in the design and application of Fallopian tube cannulation devices using the transcervical approach. Presently such cannulation systems are being used to overcome infertility disorders. These transcervical access systems are now able to displace debris that may block the tube, break down intraluminal adhesions or place egg, sperm or embryos in the tube to facilitate conception. Conversely, these same or modified devices could be used to place sclerosing agents or occlusive devices within the Fallopian tubes using similar transcervical access technology. Transcervical delivery systems incorporating a very fine endoscopic fiber have also been developed to visibly assess the inside lumen of the Fallopian tube using a transcervical approach. Such a system could be used to accurately identify specific sites in the tube for placement of such devices. The potential for placing permanent or temporary devices in the tube and the option of reversible sterilization may become a possibility in the future. One of the biggest obstacles against a wide distribution of these devices, particularly in third world countries, will be cost and the relative technical complexity in using them. These factors will need to be addressed more carefully in assessing the overall strategy of population control. The pressure on governments and international agencies to place more resources into population control may facilitate the accelerated development, application and cost containment of these new devices and delivery systems.

[Falloposcopy--a new method for evaluation and treatment of infertility due to tubal factors].

Tubal factors cause infertility in about a third of cases. With current diagnostic techniques, such as laparoscopy and hysterosalpingography, only a fraction of the causes of tubal infertility can be diagnosed and in many cases misdiagnosis results. Newer methods, such as ampullosalpingoscopy enable examination of the fimbria and ampullar segment of the fallopian tube, but the examination of the proximal tube, in which 10-20% of occlusions occur, is still impossible. We describe a new diagnostic technique, falloposcopy. It involves the transuterine insertion of a fiber optic device into the fallopian tube through a hysteroscope. This technique enables direct visualization of all segments of the fallopian tube, as well as removal of intratubal debris or adhesions. Using falloposcopy, a new grading method for tubal disease has been developed. We describe the results of 129 falloposcopic procedures in 82 women. Following falloposcopy, women with mild to moderate disease, according to the new classification, have conceived without further therapy during a follow-up period of up to 3 years. Falloposcopy may aid in differentiating between patients suitable for tubal surgery and those who should be referred for in vitro fertilization.

A prospective randomized comparison of luteal phase versus concurrent follicular phase initiation of gonadotropin-releasing hormone agonist for in vitro fertilization.

OBJECTIVE: To compare the effects of gonadotropin-releasing hormone agonist (GnRH-a) initiation either preceding or concurrent with controlled ovarian hyperstimulation (COH) in patients undergoing in vitro fertilization-embryo transfer (IVF-ET). DESIGN: Fifty-five patients were prospectively randomized to receive either GnRH-a on cycle day 21 before COH until ovarian suppression was achieved (group I) or GnRH-a concurrently with COH commencing on cycle day 3 (group II). MAIN OUTCOME MEASURES: Serum gonadotropin and ovarian steroid hormone levels, as well as fertilization, spontaneous abortion, and live birth rates. RESULTS: Twenty-six patients in group I and 29 patients in group II underwent COH for IVF-ET. Patients in group II had significantly higher serum luteinizing hormone, progesterone, and testosterone levels during stimulation with human menopausal gonadotropins (hMG) before oocyte retrieval (P < 0.05). Despite similar fertilization, biochemical, and clinical pregnancy rates, the spontaneous abortion rate was higher in group II (5/6) compared with group I (1/7) (P < 0.05). Thus, the live birth rate/retrieval for group I was 6 of 24 (25%) as compared with that of group II, which was 1 of 26 (3.8%) (P < 0.05). CONCLUSIONS: The initiation of GnRH-a in the follicular phase concurrently with hMG is associated with evidence of premature luteinization, hyperandrogenemia, and poorer pregnancy outcome compared with luteal phase administration of GnRH-a before hMG for IVF-ET.

The linear everting catheter: a nonhysteroscopic, transvaginal technique for access and microendoscopy of the fallopian tube.

The linear everting catheter is a new technology that allows for nonhysteroscopic, transvaginal access, and microendoscopy of the fallopian tube. Initial results indicate that this approach is safe, successful, and offers a number of unique advantages relative to the available alternatives. Studies are in progress to explore several of the many possible applications of this system in the diagnosis and treatment of infertile patients.

Can a single, early quantitative human chorionic gonadotropin measurement in an in vitro fertilization-gamete intrafallopian transfer program predict pregnancy outcome?

STUDY OBJECTIVE: To assess the predictive value of a single serum human chorionic gonadotropin (hCG) measurement obtained on day 14, 15, or 16 after transfer in in vitro fertilization or gamete intrafallopian transfer pregnancies. DESIGN: Retrospective. SETTING: Assisted reproductive technology (ART) programs. PATIENTS: One hundred thirty-four consecutive pregnancies from two ART programs were reviewed. RESULTS: The incidence of livebirth was only 6% when day 14 to 16 hCG values were less than 100 mIU/mL, but increased to 82% with levels greater than 100 mIU/mL (P less than 0.001). The incidence of livebirth and multiple birth correlated with rising hCG levels. Only 1% (1/71) of pregnancies with serum hCG values greater than 100 mIU/mL was ectopic, and this case was a bilateral (double) ectopic. CONCLUSIONS: A single serum hCG measurement obtained 14 to 16 days after embryo or gamete transfer not only is diagnostic but also has good predictive value for pregnancy outcome.

A prospective, randomized study of pregnancy rates after transuterotubal and intrauterine insemination.

OBJECTIVE: To assess the relative efficacy, in terms of clinical pregnancy rates (PRs), of transuterotubal insemination versus the more traditional intrauterine insemination (IUI) procedure. DESIGN: Prospective, randomized, cross-over. SETTING: University-affiliated tertiary care center. PATIENTS: One hundred sixty infertile patients underwent 414 inseminations with or without controlled ovarian hyperstimulation. INTERVENTIONS: All patients were randomized in their initial cycle to transuterotubal insemination or IUI then crossed-over in subsequent cycles (n = 191 total cycles of transuterotubal insemination and n = 223 total cycles of IUI). Transuterotubal insemination was performed initially with ultrasound guidance, and then a tactile technique was used for the last 6 months of the study. MAIN OUTCOME MEASURES: Clinical PRs and complications after both insemination methods. RESULTS: The clinical PR per treatment cycle was 7% (13/191) after transuterotubal insemination and 7% (16/223) after IUI. The overall PR per patient was 18% (29/160). The incidence of ectopic pregnancy was 1 in 191 for transuterotubal insemination cycles and 0 in 223 for IUI cycles. Other complications included 3 vasovagal episodes with transuterotubal insemination and 1 with IUI. There was no clinical evidence of tubal infection, trauma, or perforation in either group. CONCLUSION: Transuterotubal insemination did not appear to be associated with a higher PR when compared with IUI in this study. The potential for increased risk from complications related to the more invasive tubal technique does not appear to justify its use presently.

Nonhysteroscopic falloposcopy: a proposed method for visual guidance and verification of tubal cannula placement for endotuboplasty, gamete and embryo transfer procedures.

A simplified method for visualization of the uterotubal ostium using a nonhysteroscopic falloposcopic technique has been described. This transvaginal microendoscopic technique is proposed as a realistic method for the visual monitoring of tubal cannula placement for facilitating endotuboplasty, gamete and embryo transfer procedures.

Falloposcopic classification and treatment of fallopian tube lumen disease.

OBJECTIVE: To devise a diagnostic classification and scoring system for tubal lumen disease based on falloposcopy and to evaluate it against tuboplasty procedures and pregnancy outcomes. DESIGN: Prospective study approved by the hospital Institutional Review Board. SETTING: Academic tertiary infertility center. PATIENTS: Seventy-five women with hysterosalpingographic and laparoscopic evidence of endotubal disease had 112 tubes available for falloposcopic evaluation. INTERVENTION: Diagnostic and operative falloposcopy was performed, when indicated, using aquadissection, flexible wire cannulation, or direct balloon tuboplasty. RESULTS: The endotubal lumens were considered to be falloposcopically normal in 52 tubes (46%), to contain mild to moderate disease in 33 (29%), and severe to obstructive disease in 27 (25%) cases. Within a year of the procedure, 6 of the 28 women (21%) in whom at least 1 tube was normal conceived, in 2 of 22 (9%) with mild to moderate disease, and in 0 of 16 (0%) with severe endotubal disease. CONCLUSIONS: Falloposcopy provides a visual means of scoring endotubal disease and may be intrinsically therapeutic for dislodging intraluminal debris and breaking down filmy adhesions in normal or minimally diseased tubes. The presence of severe disease remains resistant to the use of current endotuboplasty treatments as reflected by poor pregnancy outcome, and such women should be provided the option of microsurgical tubal repair or in vitro fertilization and embryo transfer procedures.

Transvaginal imaging and the infertility patient.

A historical perspective and the physics and application of transvaginal imaging (TVI) for infertility investigation are presented. Pelvic anatomy, ovarian physiology, and reproductive endocrine changes as they relate to TVI for infertility processes are correlated with TVI. The transvaginal ultrasound approach for imaging reproductive organs in the management and investigation of infertility and early pregnancy is generally superior to others presently used and will play an increasingly important role in the future.

Falloposcopic observations of endotubal isthmic plugs as a cause of reversible obstruction and their histological characterization.

Eighty falloposcopies were performed in fallopian tubes of women with suspected tubal disease. In three falloposcopies (4%), isthmic plugs were observed occluding the entire isthmic lumen. In all cases these plugs were mobilized by falloposcopic-directed, selected tubal cannulation and aquadissection techniques. Restoration of tubal patency, verified by concurrent chromopertubation under laparoscopic monitoring was achieved in all cases. On one occasion, the isthmic plug was mobilized and identified on the fimbria, and tubal patency was confirmed. When this plug was retrieved and examined histologically, it was found to consist of a cast of debris containing aggregates of histiocyticlike cells of endometrial stromal or mesothelial origin. The genesis of these plugs is unknown. In another subgroup, white to yellow mucus like fragments were observed within the intramural and isthmic lumen during a further 8 of 80 falloposcopies (10%). Whether these mucus like fragments are of physiological or pathophysiological significance remains to be determined. Objective demonstration that isthmic plugs can cause reversible proximal tubal obstruction (PTO) has been achieved using falloposcopy. Falloposcopy offers the diagnostician the ability to objectively classify the cause of PTO. A useful falloposcopic classification and scoring system of tubal lumen lesions has been utilized and is described.

Falloposcopic identification of a fimbrio-ovarian mucus connection as a possible mechanism for tubal oocyte capture.

Falloposcopy combined with laparoscopy was performed in 11 women during the late follicular phase of spontaneous menstrual cycles, and a preovular follicle was confirmed to be present in each case. The fimbrial end of the tube and the ipsilateral ovary containing the preovular follicle were suspended in a fluid environment of 200 ml of lactated Ringer's solution which acted as a support medium for visualization of tubal mucus and facilitated the endoscopy procedure. As the falloposcope was passed through the fimbrial opening, it was observed to carry clear, elastic and filamentous strands of mucus material from within the distal tubal lumen in 4 of 11 procedures. As these mucus strands were carried on the tip of the falloposcope to touch the surface of the ovary containing the preovular follicle, they attached, on contact, in all cases. The fimbrio-ovarian mucus bridge created was quite strong and could be stretched for up to 7 mm before it detached from the ovarian surface. The mucus attachment appeared to be equally secure over the preovular follicle and adjacent ovarian surfaces. These fimbrio-ovarian mucus connections, which have a high affinity for ovarian surface attachment about the time of ovulation, may play an important role in securing tubal oocyte capture in humans.

Removal of cornual polyps with flexible hysteroscopy and a wire basket. A case report.

The hysteroscopic removal of large uterine polyps often can assist infertile women in conceiving. This report describes the removal of bilateral cornual polyps in a diethylstilbestrol-deformed, T-shaped uterus using a flexible operating hysteroscope and an 0.8-mm ureteral wire stone basket.

Regulation of cholesterol side-chain cleavage and 17 alpha-hydroxylase/lyase activities in proliferating human theca interna cells in long term monolayer culture.

In this report we describe the development and characterization of a long term culture system to study regulation of the expression of 17 alpha-hydroxylase, cholesterol side-chain cleavage, and 3 beta-hydroxysteroid dehydrogenase in human theca interna cells. Conditions have been established for the dispersal, growth, freezing, and storage of functional human theca interna cells isolated from preovulatory follicles of women undergoing laparoscopy for gamete intrafallopian tube transfer and in vitro fertilization procedures. Theca interna cells grown under these conditions have a doubling rate of 28-32 h and are morphologically distinct from human granulosa cells grown under the same conditions. Theca interna cells were grown, passed for successive passages, and transferred into serum-free medium containing forskolin, hCG, LH, or cAMP analogs. There was a time- and dose-dependent increase in 17 alpha-hydroxylase activity and progesterone synthesis from endogenous precursors. Added pregnenolone was converted to 17 alpha-hydroxypregnenolone, which was further converted primarily to dehydroepiandrosterone and, to a much lesser extent, androstenedione. Progesterone was converted to 17 alpha-hydroxyprogesterone and 16 alpha-hydroxyprogesterone. In studies using 17 alpha-hydroxyprogesterone as substrate, no metabolism to androstenedione or any other product was detectable. Similarly, 4-pregnen-20 alpha-ol-one (20 alpha-dihydroprogesterone) was not metabolized to any detectable products. Northern analysis performed on total RNA obtained from forskolin-stimulated theca interna cultures verified that the increase in 17 alpha-hydroxylase activity was associated with a corresponding increase in levels of mRNA specific for 17 alpha-hydroxylase cytochrome P-450. Message levels for cholesterol side-chain cleavage P-450 were similarly increased in cells treated with forskolin. No detectable mRNA encoding aromatase cytochrome P-450 was discerned. This procedure for the preparation and study of proliferating human theca internal cells provides an opportunity to study regulation of the expression of steroidogenic enzymes and other cellular processes unique to human ovarian cells.

Attitudes and anxiety levels in women conceiving through in vitro fertilization and gamete intrafallopian transfer.

Anxiety and attitudes have been examined in a series of women conceiving through in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT). Women were assessed before and after their first ultrasound examination conducted between 6 and 8 weeks' gestation. A comparison group of women attending for genetic counseling for advanced maternal age also was assessed. The results showed the two patient groups to be comparable on psychological testing. The IVF-GIFT group tended to be more concerned about a problem developing but were not more anxious. Attitude ratings showed the IVF-GIFT women to have greater investment in the pregnancy and the fetus. A comparison of scores before and after the ultrasound showed anxiety reduction for women seeing the fetal heartbeat. Attitude ratings were more positive for the women seeing the fetal heartbeat, with change less pronounced in women denied this feedback. These results confirm the effects of diagnostic testing on emotional state. Women with IVF-GIFT pregnancies show both higher concern than documented elsewhere in low-risk pregnancies, as well as greater emotional investment in the fetus.

Gonadotropin and estradiol levels during ovarian stimulation in women treated with leuprolide acetate.

Levels of FSH, LH, and estradiol (E2) were measured in the serum of 209 gonadotropin-releasing hormone analogue-treated women and in 202 control subjects during the final 5 days of ovarian stimulation in our in vitro fertilization program. Levels of FSH and E2 in serum of gonadotropin-releasing hormone analogue-treated subjects significantly exceeded control values during the sampling period, whereas LH levels were significantly lower. Concentrations of E2 in serum of gonadotropin-releasing hormone analogue-treated and control subjects were similar when corrected for differences in numbers of follicles aspirated at oocyte retrieval (mean of 8.9 and 7.2 follicles per subject, respectively). Pregnancy rates by diagnostic ultrasound were 18 and 11%, respectively, a statistically significant difference.

Interrelationships between plasma hormone levels and the content of total protein, gonadotropins and steroid hormones in antral fluids of women undergoing in vitro fertilization.

Follicle development was induced in 41 women with follicle-stimulating hormone (FSH) and human menopausal gonadotropin. Blood samples were drawn and follicular fluids (FF) were aspirated when two or more follicles attained diameters of 15 to 17 mm. Levels of estradiol (E2), progesterone (P), FSH, and luteinizing hormone (LH) were determined in samples by radioimmunoassay, and relationships between the measured parameters in antral fluids and in serum were examined by least-squares linear regression analysis. Levels of LH in serum correlated with LH and FSH levels in FF (P less than 0.005). Concentrations of FSH in serum were positively related to levels of LH, FSH, E2, and total protein in FF (P less than 0.005). E2 levels in serum were predictive of E2 levels in FF only, and levels of P in serum were directly correlated with P levels in FF (P less than 0.05). With respect to the peculiarly broad range of predictions that could be drawn from the FSH content of serum, peripheral FSH provided a better predictive index of the chemical composition of antral fluid than did the level of any other single hormone measured in serum.