John F. Kerin

Microinsert Nonincisional Hysteroscopic Sterilization

OBJECTIVE To assess the safety, effectiveness, and reliability of a tubal occlusion microinsert for permanent contraception, as well as to document patient recovery from the placement procedure and overall patient satisfaction. METHODS A cohort of 518 previously fertile women seeking sterilization participated in this prospective, phase III, international, multicenter trial. Microinsert placement was attempted in 507 women. Microinserts were placed bilaterally into the proximal fallopian tube lumens under hysteroscopic visualization in outpatient procedures. RESULTS Bilateral placement of the microinsert was achieved in 464 (92%) of 507 women. The most common reasons for failure to achieve satisfactory placement were tubal obstruction and stenosis or difficult access to the proximal tubal lumen. More than half of the women rated the average pain during the procedure as either mild or none, and 88% rated tolerance of device placement procedure as good to excellent. Average time to discharge was 80 minutes. Sixty percent of women returned to normal function within 1 day or less, and 92% missed 1 day or less of work. Three months after placement, correct microinsert placement and tubal occlusion were confirmed in 96% and 92% of cases, respectively. Comfort was rated as good to excellent by 99% of women at all follow-up visits. Ultimately, 449 of 518 women (87%) could rely on the microinsert for permanent contraception. After 9620 woman-months of exposure to intercourse, no pregnancies have been recorded. CONCLUSION This study demonstrates that hysteroscopic interval tubal sterilization with microinserts is well tolerated and results in rapid recovery, high patient satisfaction, and effective permanent contraception.

The safety and effectiveness of a new hysteroscopic method for permanent birth control: results of the first EssureTM 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.

Culture factors in relation to the success of human in vitro fertilization and embryo transfer

The development of 1-cell mouse zygotes to the blastocyst stage in vitro has been used as a quality control for the media employed for human in vitro fertilization and embryo transfer (IVF-ET). The following procedures were associated with high rates of mouse embryo development and human pregnancies following IVF-ET: adequate gassing and equilibration of the medium, double rinsing of pipettes and catheters used to handle embryos, use of a HEPES-buffered medium for manipulating embryos in the absence of an atmosphere containing 5% CO2, control of excessive temperature in the vicinity of the embryos, and ET using medium containing 50% patients serum. The institution of these procedures gave more consistent pregnancy rates. However, there was no obvious association between fertilization and cleavage of human oocytes and the quality of the medium ascertained by the mouse embryo development test.

Pregnancy-related chemotactic activity of human follicular fluid *

We measured chemotactic activity in 238 follicular fluids (FF) aspirated from 45 women who had undergone ovarian stimulation with a combination of clomiphene citrate and human menopausal gonadotropin for oocyte retrieval, in vitro fertilization, and embryo transfer. Fifteen of the treatment cycles resulted in pregnancy. The mean chemotactic activity, measured as the distance in microns granulocytic leukocytes migrated through a 3.0-micron membrane, was significantly higher in FF from conceptual cycles, compared with nonconceptual cycles. Serum chemotactic activity was significantly lower in conceptual cycles, compared with nonconceptual cycles. A chemotactic gradient appears to exist between the peripheral circulation and the ovarian follicle. The gradient favors the follicle in conceptual cycles, as indicated by the chemotactic quotient (the ratio of chemotactic activity of FF to serum). In conceptual cycles the chemotactic quotient was 1.7 +/- 0.17, compared with 0.7 +/- 0.03 for nonconceptual cycles. The presence of leukocyte chemotactic factor in FF appears to discriminate prospectively with a 90% degree of confidence between conceptual and nonconceptual in vitro fertilization and embryo transfer cycles.

Essure hysteroscopic sterilization: Results based on utilizing a new coil catheter delivery system

STUDY OBJECTIVE To assess the safety and placement effectiveness of a new delivery catheter for the Essure micro-insert hysteroscopic sterilization system. DESIGN Prospective, multicenter, single-arm clinical study. (Canadian Task Force classification II-3). SETTING Hospital-based clinical research centers. PATIENTS One hundred two women of reproductive age and proven fertility. INTERVENTION A new coil catheter delivery system was used for micro-insert placement. MEASUREMENTS AND MAIN RESULTS The bilateral placement of micro-inserts using the coil catheter delivery system occurred in 100 women out of 102 attempts (98%). The two women who did not have successful micro-insert placement were subsequently shown to have proximal tubal stenotic disease. CONCLUSION These findings indicate that the introduction of the coil catheter delivery system for Essure hysteroscopic sterilization improves the micro-insert bilateral placement rate when compared with previous studies. It is hypothesized that the coil catheter has superior navigational properties, particularly within tortuous or narrowed tubal lumens.

The Influence of Insemination Timing and Semen Characteristics on the Efficiency of a Donor Insemination Program

The analysis of accumulated data from conceptional and nonconceptional ovulatory menstrual cycles of patients undertaking artificial donor insemination has allowed some observations to be made on the practical aspects which may influence the efficiency of the program. The evidence suggests that with the use of preserved semen, accurate timing of insemination is essential, and that days 0 and +1 with respect to the luteinizing hormone surge appear to be advantageous as compared with closely related days. When the numbers of motile spermatozoa which were inseminated over a critical 4-day interval were analyzed, the results also suggested that improved conception rates occurred when larger numbers of active spermatozoa were used. A comparison was made between those patients who had been inseminated on a single occasion and those inseminated on more than one occasion during the periovulatory period. The results obtained from those cycles inseminated on a single occasion were inferior to those obtained from cycles inseminated more than once. Finally, some limited comparison is drawn between the established insemination programs of bovine husbandry and the relatively inefficient human experience. One explanation may lie in the wider spectrum of donor semen desirable for the human programs.

Linear and quantitative migration of stored sperm through cervical mucus during the periovular period.

The ability of stored spermatozoa to penetrate fresh samples of cervical mucus obtained from 23 patients during 47 menstrual cycles was studied, utilizing an in vitro test. The determination of daily hormonal and gonadotropin values allowed an accurate realationship to be established between the results of sperm-mucus interaction and the environmental milieu. Cervical mucus was found to be effectively penetrable only on day −1 and day 0 when considered with respect to the plasma luteinizing hormone surge. Correlation was apparent between the ability of sperm to penetrate and the favorable clinical parameters of cervical assessment.

Endocrinology of Ovarian Stimulation for In Vitro Fertilization

Summary: Understanding of the endocrinology of in vitro fertilization has advanced rapidly in the past 5 years. Despite a multitude of ovarian stimulation regimens a particular regimen has not demonstrated a marked superiority. In principle the achievement of high FSH levels during the early follicular phase to recruit a maximum number of follicles with a tolerable degree of asynchrony for final maturation is confined to a limited time span or ‘FSH window’ of about 3 to 4 days before negative E2 feedback induces below‐threshold FSH levels, thereby condemning all subsequent follicles in that cycle to atresia. It appears that one can widen and/or amplify the ‘FSH window’ too far from gross hyperstimulation resulting in the recruitment of many follicles with an intolerable degree of asynchrony. This may lead to a defective endocrine environment for the oocytes contained within these follicles or an abnormal luteal environment and an increased frequency of fertilization, cleavage and implantation failure.

Acute adnexal torsion before oocyte retrieval in an in vitro fertilization cycle

The use of controlled superovulation protocols means that many otherwise healthy women spend some time with enlarged, multicystic ovaries that are at risk for torsion. A large series suggested that the incidence of adnexal torsion in IVF cycles is approximately 0.1% (1). Most such torsions occur after ET, usually in the setting of ovarian hyperstimulation syndrome. We report a case of adnexal torsion that occurred before oocyte retrieval in an IVF cycle. The patient was a 37-year-old nulligravid woman whose husband was azoospermic secondary to congenital bilateral absence of the vas deferens. Previous investigation by laparoscopy, hysteroscopy, and falloposcopy revealed normal findings. In three previous IVF cycles, normal fertilization was achieved with intracytoplasmic sperm injection with fresh epididymal sperm in a total of 33 (75%) of 44 oocytes; the fertilization rates were 82%, 83%, and 60% in the three cycles. During the study cycle, she underwent stimulation with 150 IU/d of recombinant human FSH (Gonal-F; Serono, Sydney, Australia). On day 12 of stimulation, sonography of the left ovary showed nine follicles of 18 mm in mean diameter and six smaller follicles (,16 mm in mean diameter); the right ovary had seven follicles of 18 mm in mean diameter and nine smaller follicles. An IM injection of 5,000 IU of hCG (Profasi; Serono) was administered at 9:00 P.M. on day 12 and oocyte retrieval was scheduled for 9:00 A.M. on day 14. Early on the morning of day 14, the patient had the sudden onset of severe lower left-sided abdominal pain with nausea but no emesis. On presentation at 8:00 A.M., she was tachycardic (104 beats/min) but afebrile and stable. Physical examination revealed lower abdominal tenderness that was worse on the left side and no signs of peritonitis. A differential diagnosis of either acute hemorrhage into, or torsion of, the left ovary was made, and oocyte retrieval proceeded at 9:00 A.M. Intraoperative sonography showed the left ovary positioned high in the midline; there was no free fluid or other abnormality. Unfortunately, Doppler ultrasound was not available. Transvaginal oocyte retrieval was undertaken in the hope that emptying the ovaries would allow the ovary with subacute torsion to return to its anatomic position. Seven oocytes were retrieved from the left ovary; the follicular fluid from all those follicles was densely bloodstained. Twelve oocytes were obtained from the right ovary; the follicular fluid from all those follicles was clear. After the procedure, the patient’s symptoms worsened; laparoscopy was performed 2 hours later and revealed torsion of the left ovary. The ovary was detorsed under laparoscopic control and peritoneal lavage with warmed saline solution was undertaken. During 15 minutes of observation, the left adnexal structures regained a more normal appearance. A comparison of the performance of the oocytes obtained from each ovary is presented in Table 1. The patient’s clinical symptoms resolved quickly and transcervical transfer of three embryos created from oocytes retrieved from the right ovary was performed on day 16. Luteal endocrine parameters were normal and 500-IU doses of hCG were given on days 18 and 21. Unfortunately, pregnancy did not ensue.

Gonadotropin and Estradiol Levels During Ovarian Stimulation in Women Treated With Leuprolide Acetate

&NA; 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. (Obstet Gynecol 73:990, 1989)