Air bubble migration is a random event post embryo transfer.

INTRODUCTION: Air bubble location following embryo transfer (ET) is the presumable placement spot of embryos. The purpose of this study was to document endometrial air bubble position and migration following embryo transfer. DESIGN: Multicenter prospective case study. MATERIALS AND METHODS: Eighty-eight embryo transfers were performed under abdominal ultrasound guidance in two countries by two authors. A single or double air bubble was loaded with the embryos using a soft, coaxial, end opened catheters. The embryos were slowly injected 10-20 mm from the fundus. Air bubble position was recorded immediately, 30 minutes later and when the patient stood up. RESULTS: Bubble marker location analysis revealed a random distribution without visible gravity effect when the patients stood up. The bubble markers demonstrated splitting, moving in all directions and dispersion. CONCLUSION: Air bubbles move and split frequently post ET with the patient in the horizontal position, suggestive of active uterine contractions. Bubble migration analysis supports a rather random movement of the bubbles and possibly the embryos. Standing up changed somewhat bubble configuration and distribution in the uterine cavity. Gravity related bubble motion was uncommon, suggesting that horizontal rest post ET may not be necessary. This report challenges the common belief that a very accurate ultrasound guided embryo placement is mandatory. The very random bubble movement observed in this two-center study suggests that a large "window" of embryo placement maybe present.

GnRHa flare and IVF pregnancy rates.

OBJECTIVES: GnRH agonist administered early in the menstrual cycle (flare) causes an endogenous discharge of FSH and LH. Flare has been used in conjunction with gonadotropin ovarian stimulation for IVF 'poor responders'. There is an ongoing controversy regarding whether flare protocols improve pregnancy rates in 'poor responders'. The current study was designed to compare a GnRHa flare protocol with long suppression GnRHa IVF in 'poor responders'. METHODS: Seventy-three newly diagnosed poor responders who failed long GnRHa suppression IVF attempts were compared retrospectively with 128 age-matched IVF patients previously known poor ovarian responders treated with a long GnRHa suppression protocol. 'Poor responders' consisted of patients with peak E(2) less than 1000 pg/ml and/or less than five mature follicles with diameter >15 mm on the day of hCG administration. Student's t-test was used to analyze the data and the chi-squared test was used to compare fertilization and pregnancy rates. RESULTS: The flare protocol produced higher peak E(2) levels (1647+/-747 vs. 720+/-258 mIU/ml, P<0.05) and a larger number of mature follicles (5.8+/-2.2 vs. 4.0+/-1.0 P<0.05) in the study vs. the control group. A 30% pregnancy rate was achieved during this second IVF attempt using GnRHa flare protocol in the study group vs. 37 in the control group (P>0.05, NS). CONCLUSIONS: A comparison between the flare protocol group and the age-matched control group of poor ovarian responders subject to down regulation protocol, revealed higher peak E(2) levels and more mature follicles, respectively. However, both groups yielded comparable pregnancy rates. The use of high dose gonadotropin treatment in our study groups seems to be the only explanation for their subsequent successful outcome. We concluded that GnRH agonist flare protocol does not result in better IVF outcome compared with long GnRH agonist suppression protocol in IVF poor responders.

Investigation of the uterine cavity and fallopian tubes using three-dimensional saline sonohysterosalpingography.

OBJECTIVE: To compare three-dimensional saline sonohysterosalpingography (SHSG) to X-ray hysterosalpingography (HSG) for the evaluation of the uterine cavity and fallopian tubes. PATIENT POPULATION: Fifteen infertile women on whom X-ray HSG had been performed within 1 year prior to this study. METHOD: Fifteen infertile women underwent three-dimensional power Doppler examination of the uterus and fallopian tubes with three-dimensional SHSG during the follicular phase. Distension was achieved using sterile saline injected through a 5 French HSG catheter. Peritoneal accumulation of free fluid surrounding the ovary and tube was required for a diagnosis of a patent tube. Fluid accumulation in the cul-de-sac without visualization of the tubes was considered consistent with at least one tube being patent. RESULTS: three-dimensional saline SHSG was completed in 14 patients. One patient had cervical stenosis and the procedure could not be performed. No significant intrauterine pathology was identified by either X-ray HSG or sonography. Three-dimensional saline SHSG made false positive diagnoses of tubal occlusion in four out of seven fallopian tubes (57%). The sensitivity and specificity for detecting tubal occlusion was 75 and 83%, respectively, with a positive predictive value of 40% and negative predictive value of 95%. Detection of fallopian tube architecture was not possible with three-dimensional saline SHSG in any patient. Simultaneous use of three-dimensional Doppler did not clearly identify the flow of saline through the fallopian tubes. CONCLUSIONS: Transvaginal three-dimensional saline SHSG provides good visualization of the uterine cavity and myometrial walls in three orthogonal planes. However, it does not diagnose tubal occlusion or depict architecture of the fallopian tube as accurately as X-ray HSG. Although we were able to visualize the distal fallopian tube and fimbria with real-time imaging, we were not able to satisfactorily image the proximal tube with three-dimensional power Doppler. This technique may be reserved as an initial screening test to evaluate the uterine cavity and test patency. Patients at high risk for tubal disease by history or with suspected tubal occlusion on three-dimensional saline SHSG should be evaluated by either X-ray HSG or laparoscopy with chromopertubation. Further improvements of three-dimensional technology and contrast materials will, it is hoped, make this method comparable to X-ray HSG.

Recurrent triploidy of maternal origin.

We report the occurrence of triploid preimplantation embryos following in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in a woman with two previously-identified triploid conceptuses which spontaneously underwent fetal demise at 10 and 23 weeks' gestation. An error in maternal meiosis II is proposed as the most likely cause.

Diagnostic and operative microlaparoscopy: a preliminary multicentre report.

Microlaparoscopes have been evaluated for minimally invasive laparoscopy using minimal anaesthesia or analgesia since our preliminary report on microlaparoscopy in 1993. This international multicentre report of safety and efficacy of diagnostic and operative microlaparoscopy was completed to evaluate the role of microlaparoscopy in a wide spectrum of gynaecological indications, diagnoses of pelvic and tubal disease, tubal occlusion and assisted reproduction. A total of 408 patients from seven centres around the world were included in this report. Of the 164 patients who underwent microlaparoscopy under local analgesia only three patients (1.8%) converted to i.v. sedation because of pain intolerance. All 71 patients who underwent microlaparoscopy under i.v. sedation as planned tolerated the procedure with acceptable pain level perception. Only one abdominal wall minor bleeding and one uterine wall minor bleeding were recorded in the remaining 173 patients who underwent microlaparoscopy under general anaesthesia. Visualization of the pelvic organs was sufficient in all 408 cases for diagnosis and treatment of selected pelvic pathology. We concluded, based on this sizeable microlaparoscopy series, that this outpatient procedure can replace large diameter laparoscopy for diagnosis and treatment of various pelvic conditions. Microlaparoscopy can safely replace large diameter laparoscopy in motivated patients who require minor operative procedures such as tubal occlusion, minor adhesiolysis, tubal gamete or embryo transfers and fulguration of endometriotic implants. This series demonstrated that operative microlaparoscopy can be carried out under general anaesthesia, reducing to nil the potential damage of a large diameter tracer. Future improvements in i.v. sedation in combination with i.p. local anaesthesia will potentially eliminate the need for general anaesthesia in some of the patients undergoing minor operative microlaparoscopy.

The effect of the oviduct, uterine, and in vitro environments on zona thinning in the mouse embryo.

OBJECTIVE: To evaluate the impact of the oviduct, uterine, and in vitro environments on zona pellucida thinning in the mouse embryo. DESIGN: Female mice were stimulated with pregnant mare serum gonadotropin and mated and hCG injection. Unilateral oviduct ligation was performed on day 2 of gestation using the dorsal approach. The mice were divided into equal groups and killed on days 2, 3, 4, 5, and 10 of gestation. In vitro incubated embryos served as controls. Average daily zona thickness measurements were subjected to analysis of variance and paired Student's t-test. SETTING: The laboratory of the assisted reproductive program of Rush University Medical Center. MAIN OUTCOME MEASURE(S): Progressive daily decrease in average zona thickness. RESULT(S): Zona measurements of embryos flushed out of uterine horns, ligated oviducts, and in vitro incubation demonstrated statistically significant decreases in zona thickness, from 9.6 +/- 1.6 microns (day 3) to 6.0 +/- 0.8 microns (day 5), from 11.6 +/- 2.2 microns (day 2) to 6.0 +/- 1.6 microns (day 5), and from 11.1 +/- 2.0 microns (day 2) to 6.0 +/- 1.6 microns (day 5), respectively. There were no differences in average zona thickness for embryos in the same cell stage and same protocol day in all three locations. CONCLUSION(S): Zona thinning seems to be induced primarily by the dividing embryo before implantation. A substantial tubal and uterine contribution to zona thinning was not detected in this mouse embryo model.

Glass wool column filtration versus mini-Percoll gradient for processing poor quality semen samples.

OBJECTIVE: To compare the quality and number of spermatozoa recovered from laboratory-induced severe oligozoospermic specimens processed by mini-Percoll gradient and glass wool column filtration. DESIGN: Both sperm-processing procedures were compared in similar sperm samples adjusted to contain equal low numbers of motile spermatozoa using either dilution (oligozoospermia) or with the addition of killed sperm (oligoasthenozoospermia). The spermatozoa processed by both procedures samples were evaluated for motility, response to hypo-osmotic swelling test, and the hemizona assay. PATIENTS: Five healthy fertile sperm donors. SETTING: Private Andrology Laboratory and University Hospital. MAIN OUTCOME MEASURE: Sperm motility, hypo-osmotic swelling test, and hemizona assay results determined the efficacy of the sperm-processing procedures. RESULTS: The concentration of sperm recovered after both procedures was not affected by either preparation or processing methods. Glass wool-processed sperm had higher motility in oligoasthenozoospermic samples, bound tightly to hemizonae in higher mean numbers, and demonstrated a higher percentage of membrane-intact spermatozoa in oligozoospermic samples. CONCLUSION: Laboratory-prepared oligozoospermic samples subjected to glass wool filtration yielded more functionally intact spermatozoa than mini-Percoll gradient processing.

Sonographically monitored ovarian stimulation for assisted reproduction: a prospective, blind study.

OBJECTIVE: To assess prospectively the appropriateness of follicular sonography alone for monitoring ovarian stimulation and to compare it to ovarian monitoring with both follicular sonography and hormone level determinations. STUDY DESIGN: Prospective, blind, clinical study in which the investigator made cycle management decisions based on follicular sonography only. RESULTS: Follicular sonography alone predicted 88% of the decisions made by the combination of follicular sonography, luteinizing hormone (LH), estradiol (E2) and progesterone measurements. Follicular sonography was unable to predict abnormal E2 patterns in eight (8%) of the patients' scans. Follicular sonography did not detect three (3%) patients with a premature LH surge. CONCLUSION: Follicular sonograms alone performed during ovarian stimulation predicted 88% of cycle decisions. One could argue that hormone measurements could be either reduced or eliminated during ovarian stimulation for assisted reproductive technology and that follicular sonography only would be a cost-effective compromise. The effect of such simplified monitoring on pregnancy rates would require further prospective evaluation.

A system for simultaneous bilateral tubal cannulation.

OBJECTIVE: The efficacy of a new system for simultaneous bilateral tubal cannulation under tactile impression was evaluated. METHODS: Two radiologically detectable selective salpingography catheters (Bard Gynecology and Urology, Covington, GA) were glued back to back in a "T" configuration similar to an intrauterine device. A sliding plastic sleeve contained the straightened catheters and the uterus was cannulated under tactile impression. The sleeve was then withdrawn and the catheters opened within the uterine cavity and wedged into the right and left tubal ostia simultaneously. Selective injection of water-soluble radiologic contrast material into the tubes resulted in selective salpingography and determined successful tubal cannulation. Withdrawal of the catheters back into the sleeve allowed injection of contrast material into the uterine cavity. PATIENTS: The system was evaluated in 14 consenting patients scheduled for hysterosalpingogram during infertility evaluation. RESULTS: Bilateral selective salpingography was achieved successfully under tactile impression in 12/14 (86%) patients. In two patients with either distorted or very small uterine cavity, the catheter tips embedded into the lateral uterine walls and did not selectively cannulate the tubal ostia. Reapplication of the system under fluoroscopy allowed bilateral selective salpingography of these two patients. CONCLUSION: Simultaneous bilateral selective salpingography eliminated the need for cervical cannula, significantly reduced fluoroscopy time to seconds, and demonstrated that tactile cannulation is successful in normal uteri. Application of this system for simultaneous tubal cannulation is identical to intratubal uterine device insertion, a procedure familiar to all gynecologists. Therefore, this catheter system may further contribute to simplification of transcervical access into the fallopian tubes for diagnosis and treatment.

Selective salpingography for the diagnosis and treatment of early tubal pregnancy.

OBJECTIVE: To determine whether selective salpingography can accurately diagnose and treat patients with early ectopic pregnancies (EPs). DESIGN: Prospective clinical case study. SETTING: Selective salpingography was performed in an outpatient setting under i.v. sedation. PATIENTS: Selective salpingography was performed in 10 women who had clinical presentation suggestive of EP, two consecutive abnormal hCG measurements < 2,000 mIU/mL, and inconclusive vaginal probe sonogram. INTERVENTION: Selective salpingography was performed under fluoroscopy. A cervical cannula was placed, and the tubal ostium was cannulated with a curved selective salpingography catheter (Bard Gynecology and Radiology, Covington, GA). Methotrexate (MTX) (25 or 50 mg) was injected into the affected tube through the selective salpingography catheter. MAIN OUTCOME MEASURE: The accuracy of selective salpingography in the diagnosis of early EP was determined by the rate of fluoroscopic imaging of an ampullary radiolucency upon injection of contrast material through the selective salpingography catheter. Resolution of the EP after injection of MTX into the tube was detected by serial declining hCG measurements. RESULTS: Selective injection of contrast material into the fallopian tubes detected seven ampullary pregnancies in 10 patients. Two patients demonstrated neither tubal pregnancy nor intrauterine pregnancy. One patient with apparent bilateral proximal cornual occlusions on selective salpingography underwent laparoscopy, followed by salpingostomy of an ampullary pregnancy. All 7 patients who received MTX through the selective salpingography catheter completely resolved the EP. Four patients demonstrated patent fallopian tubes on hysterosalpingograms performed 3 to 6 months later. CONCLUSION: Selective salpingography may diagnose early tubal pregnancies of some patients with equivocal clinical, laboratory, and sonographic findings. These patients can be successfully treated at the same time with a single dose of MTX delivered into the affected tube. Selective salpingography reduced the need for laparoscopy and operative intervention. Selective salpingography is a simple and relatively inexpensive diagnostic and therapeutic alternative in patients with suspected early tubal pregnancy.

Microlaparoscopy: a preliminary report.

A series of 30 microlaparoscopies performed under local anaesthesia and sedation are presented. The visualization of the pelvic organs was acceptable and the patients reported mild discomfort only. Microlaparoscopy may potentially replace macrolaparoscopy in selected cases.

Transcervical tubal cannulation, past, present, and future.

OBJECTIVE: To evaluate publications that introduced novel diagnostic and therapeutic transcervical procedures on the fallopian tubes. DESIGN: Major studies that conceptually changed the therapeutic approach to the fallopian tubes were reviewed. Minor publications were also included if they introduced a new concept or contributed to the topic. Clinical publications were selected if they involved transcervical diagnosis and treatment of fallopian tubes. RESULTS: Transcervical tubal catheterization procedures for diagnosis of tubal disease, tubal obliteration, tubal recanalization, and tubal medication are minimally invasive procedures that can improve our understanding and diagnostic accuracy of tubal disease. These procedures allow transcervical treatment of proximal tubal occlusion. Further improvements in equipment and methodology are promising. Transcervical tubal occlusion, gamete and embryo deposition, and treatment of ectopic pregnancy may all be performed using the transcervical approach. CONCLUSION: Transcervical tubal catheterization can replace microsurgery and IVF in selected patients with proximal tubal occlusion, improve the diagnostic accuracy of tubal disease, and deliver medications to the fallopian tubes. Cumulative knowledge suggests that transcervical tubal catheterization should become a universally accepted, taught, and practiced approach in the diagnosis and treatment of the fallopian tubes.

The multicentre transcervical balloon tuboplasty study: conclusions and comparison to alternative technologies.

Transvaginal tubal catheterization procedures have been suggested as an alternative to microsurgery and in-vitro fertilization (IVF) in the treatment of women with proximal tubal occlusion. A transcervical balloon tuboplasty (TBT) catheter was specifically developed and tested in a prospective multicentre trial. A total of 151 women with confirmed bilateral or unilateral tubal occlusion were studied. The primary study population included 106 women who, after exclusion of patients for protocol violations, represented those females who were treated for complete tubal occlusion with TBT. TBT is an ambulatory, minimally invasive catheter procedure, performed under paracervical block or mild sedation, which utilizes a co-axial balloon catheter under fluoroscopic guidance. Re-canalization, pregnancy and reocclusion rates following the procedure were documented. A total of 28 patients demonstrating uni- or bilateral tubal patency after either hysterosalpingography and/or selective salpingography represented the control population. TBT established tubal patency of at least one Fallopian tube in 95/106 patients (90%) and in 167/205 obstructed oviducts (82%). Clinical pregnancies occurred in 37/106 females (35%), with a life table adjusted rate of 37%. Patients without distal disease had significantly higher pregnancy rates than those with bipolar tubal disease (49% versus 12%, life table adjusted rate; P = 0.0002) but pregnancy rates were independent of underlying aetiology for tubal disease. Pregnancy rates in control patients who did not reach TBT because of tubal patency after hysterosalpingography and/or selective salpingography were significantly lower than in those successful treated with TBT (P = 0.027), and occurred only for four cycles after hysterosalpingography and with approximately a 1 year delay after selective salpingography.(ABSTRACT TRUNCATED AT 250 WORDS)

Sonographic transcervical balloon tuboplasty.

The purpose of this study was to evaluate sonographic guidance for transcervical tubal catheterization and transcervical balloon tuboplasty of patients with bilateral proximal tubal occlusion. Cornual catheterization and transcervical balloon tuboplasty were performed under sonographic guidance. Injection of micro-bubble emulsion confirmed tubal recanalization. Tubal patency demonstrated by sonography was confirmed by injection of contrast material under fluoroscopy. Four women with bilateral proximal tubal occlusion confirmed by previous hysterosalpingogram and laparoscopy underwent sonographically guided transcervical balloon tuboplasty. Patients with distal or peritubal damage were excluded from this study. Bilateral tubal patency confirmed by sonography and subsequent fluoroscopy was achieved in all four patients. One patient conceived spontaneously, a month following the procedure, and delivered at term. Sonographically guided transcervical balloon tuboplasty can be performed successfully on patients with proximal tubal occlusion. Identification of the catheter tip and successful cannulation of the internal tubal ostia were easier to perform under fluoroscopy. Further improvements in sonographic equipment and catheter technology will hopefully eliminate radiation and replace fluoroscopy during the performance of transcervical balloon tuboplasty. Sonographic transcervical tubal catheterization may, therefore, become a simple and cost-effective procedure for the diagnosis and treatment of patients with proximal tubal occlusion.

Tubal factors in infertility.

Proximal, distal, and peritubal damage can be caused by a number of pathologic processes such as inflammation, endometriosis, and surgical trauma. The diagnosis of tubal occlusion relies primarily on hysterosalpingography, hysteroscopy, and laparoscopy. A number of innovative diagnostic procedures such as sonosalpingography, falloposcopy, and selective salpingography improved our ability to accurately diagnose tubal pathology. The long-standing surgical corrective approach to treat tubal occlusion has been replaced by noninvasive methods in selected patients with endoluminal damage. The development of noninvasive transcervical catheter methods to recanalize proximally obstructed fallopian tubes also allows access to the fallopian tubes for deposition of gametes and embryos and improves the diagnosis and treatment of tubal pregnancies. Transcervical tubal cannulation reduces the risks, costs, and morbidity of surgical procedures. The diverse applications of the transcervical tubal approach may also replace surgical invasive procedures in assisted reproductive procedures. Although radical changes have occurred in the treatment of proximal tubal occlusion, the repair of distal and peritubal damage frequently yields disappointing results, and will probably remain the challenge of the 1990s.

Pooled sequential ejaculates: a way to increase the total number of motile sperm from oligozoospermic men.

We investigated the yield of total number of motile spermatozoa from oligozoospermic men by pooling two closely spaced sequential ejaculates. Semen characteristics were compared between sequential ejaculates (within a period of 1 to 4 hours) of 18 oligozoospermic males (sperm concentration less than 20 X 10(6)/mL and total sperm count less than 40 X 10(6) in the ejaculate) and a control group of 16 normozoospermic men. Whereas the median total number of motile sperm of normozoospermic males significantly decreased from 70 X 10(6) in the first ejaculate to 23 X 10(6) in the second sequential ejaculate, such a decrease was not detected in oligozoospermic males, 3.6 X 10(6) and 3.1 X 10(6), respectively. The percent of normozoospermic and oligozoospermic men who demonstrated a decreased (less than 50%), a comparable (50% to 150%), or an increased (greater than 150%) total motile sperm count in the second ejaculate in comparison with the first ejaculate were 69%, 31%, and 0 versus 39%, 28%, and 33%, respectively. Consequently, pooling of two sequential ejaculates significantly increased the median total number of motile sperm from normozoospermic males by 144% and from oligozoospermic males by 329%, (to 10.2 X 10(6]. We suggest that pooling of two sequential ejaculates from oligozoospermic males is a simple and cost effective method to increase significantly the total number of motile sperm for intrauterine insemination, in vitro fertilization, gamete intrafallopian transfer, or semen cryopreservation.

Transcervical balloon tuboplasty. A multicenter study.

Transcervical balloon tuboplasty represents a noninvasive technique to treat proximal tubal occlusion. In a multicenter study, 77 women with confirmed bilateral proximal tubal occlusion underwent the procedure. In 71 patients (92%), at least one proximally obstructed fallopian tube was recanalized. Concomitant distal bilateral tubal occlusions were diagnosed after successful proximal tubal balloon recanalizations in 13 patients (17%). In the remaining 64 patients, 22 clinical pregnancies (34%) have been confirmed during a median follow-up period of 12 months. Among those, 17 (77%) resulted in normal deliveries and five (23%) resulted in a first-trimester miscarriage. One patient was diagnosed with an ectopic pregnancy. Among 25 patients who had not conceived within 6 months of the procedure, 17 (68%) demonstrated continuing tubal patency on repeated hysterosalpingogram. We conclude that transcervical balloon tuboplasty is a safe outpatient technique that may represent an alternative to in vitro fertilization or microsurgical reanastomosis of fallopian tubes.

Ovarian stimulation protocol for in vitro fertilization with gonadotropin-releasing hormone agonist widens the implantation window.

Pregnancy rates vary considerably with the type of ovarian stimulation used for in vitro fertilization and embryo transfer (IVF-ET). The window of implantation may represent one of the rate-limiting steps in IVF success. We therefore investigated estimated implantation times of 10 consecutive IVF singleton pregnancies, achieved using pituitary suppression with gonadotropin-releasing hormone agonist (GnRH-a) before and during ovarian stimulation with human menopausal gonadotropins (hMG), and compared those with 9 consecutive IVF pregnancies achieved by hMG stimulation only. Estimated implantation times were calculated by regression analysis of serial human chorionic gonadotropin (hCG) measurements between days 7 and 16 after ET. The GnRH-a/hMG pregnancies implanted between days 7 and 11, whereas hMG pregnancies implanted between days 7 and 9 after ET. The hCG regression curve for the GnRH-a/hMG pregnancies revealed a delay of 1.5 days in estimated implantation time compared with the hMG only group. There were no significant differences in pretransfer in vitro embryos development between the two groups. Thus, the delay in hCG rise probably reflects a delay in embryo implantation. We therefore conclude that a GnRH-a/hMG stimulation protocol appears to widen the implantation window in comparison with a hMG only protocol. This observation may at least in part explain the improved IVF pregnancy success with GnRH-a/hMG stimulation protocols.