Ultrasound-guided soft catheter embryo transfers will improve pregnancy rates in in-vitro fertilization.

Attempts to improve clinical pregnancy rates after in-vitro fertilization (IVF) and embryo transfer are constantly being made. Two changes in technique of embryo transfer of potential clinical importance were evaluated over two contiguous time periods in order to observe any corresponding change in clinical pregnancy (CP) rate per transfer: (i) embryo transfer catheter; (ii) ultrasound guidance. Catheter choices were hard: Tefcat, Tom Cat, or Norfolk; or soft: Frydman or Wallace. Ultrasound visualization was considered to be excellent/good when the catheter could be followed from the cervix to the fundus by transabdominal ultrasound with retention of the embryo-containing fluid droplet; fair/poor if visualization could not document the sequence of events. Embryo transfers were performed in 518 cycles. CP rates per transfer using soft and hard catheters was 36 and 17% (P < 0.000) respectively. CP rates per transfer for transfers performed with and without ultrasound guidance were 38 and 25% (P < 0.002) respectively. A statistically significant difference was also noted when visualization ranks were compared. CP rates per transfer in all excellent/good ultrasound-guided transfers was 41.5 versus 16.7% for fair/poor transfers (P < 0.038). In conclusion, performance of embryo transfer with a soft catheter under ultrasound guidance with good visualization resulted in a significant increase in clinical pregnancy rates.

Inhibin-B as a test of ovarian reserve for infertile women.

The objective of the study was to compare a standard clomiphene citrate challenge test with inhibin-B serum concentrations also obtained on cycle days 3 and 10 as a negative predictor of pregnancy in a group of 106 women at risk for compromised ovarian function. Mean duration of follow-up was 8.25 months in 95 patients with 30 pregnancies recorded (plus one biochemical). Inhibin-B concentrations on cycle days 3 and 10 were correlated only with each other and not with serum oestradiol, follicle stimulating hormone (FSH) and/or pregnancy rates. Pregnancy occurred in 34.5% (10/29) of all patients with inhibin-B values >/=45 pg/ml on cycle day 3 and in 31.8% (21/66) of those with values <45 pg/ml. For FSH >11 mIU/ml on either day, pregnancy rate was 13.6% versus 38.4% for FSH of

Ovarian response to gonadotrophins, optimal method for oocyte retrieval and pregnancy outcome in patients with vaginal agenesis.

The aim of this study is to characterize the ovarian response to stimulation and the optimal method of oocyte retrieval in patients with vaginal agenesis (Mayer- Rokitansky-Küster-Hauser syndrome) in a gestational carrier programme. Twelve patients underwent gonadotrophin stimulation and hormonal monitoring. Forty-nine treatment cycles were initiated; seven cycles were cancelled secondary to poor stimulation. Five patients had undergone surgical neovagina construction; seven patients had utilized vaginal dilators. Oocyte retrieval was achieved in one cycle via transvesical ultrasound, in two cycles via transabdominal ultrasound, in nine cycles via laparoscopy and in 30 cycles via transvaginal ultrasound. Ten pregnancies were achieved which included two clinical pregnancies, two biochemical pregnancies, three singleton births and three sets of twin births. A live birth rate of 45.5% was achieved per patient. Hormonal response to gonadotrophin stimulation in this population was similar to that of patients with normal pelvic anatomy. Pregnancy outcome was comparable to other patients utilizing gestational carriers within the same program (i.e. surgically absent uterus, anatomically non-functioning uterus, etc.). The surgical creation of a neovagina makes transvaginal retrieval technically more difficult than when dealing with a dilator-created vagina, and may require laparoscopy or transabdominal ultrasound for oocyte retrieval.

Live birth from a zygote cryopreserved for 8 years.

After a cryopreservation period of 8 years, four zygotes were thawed and transferred to the patient's uterine cavity. A singleton pregnancy resulted in the delivery of a normal male. This case report offers evidence that long terms of cryopreservation are consistent with full developmental potential post-thaw, and encourages further examination of imposing limits on length of storage of frozen concepti.

Association of positive Chlamydia trachomatis and Chlamydia pneumoniae immunoglobulin-gamma titers with increasing age.

STUDY OBJECTIVES: To use Chlamydia trachomatis immunoglobulin-gamma (IgG) titers to investigate the possibility of their association with ovarian cancer, and to evaluate the effectiveness of this titer in algorithmic protocols in infertility. DESIGN: Prospective, age-matched, pilot study (Canadian Task Force classification II-2). SETTING: University and university-affiliated office practice. PATIENTS: The original 30 patients were seen for follow-up of ovarian cancer (19) and at yearly examination for nonmalignant disease (10). An additional group of 21 women seen for pelvic pain and infertility was added to clarify questions that arose during the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Chlamydia trachomatis IgG titers were positive in 15 (79%) of 19 of women with ovarian cancer, 9 (90%) of 10 age-matched controls, and 14 (67%) of 21 patients with infertility and pain. When analyzed by age, 4 (40%) of 10 patients under 30 years and 34 (85%) of 40 patients 30 years of age or older had positive titers (p = 0.007). Of 21 women with positive Chlamydia pneumoniae titers, 17 (81 %) had positive C. trachomatis titers, and 17 (85%) of 20 with positive C. trachomatis titers had positive C. pneumoniae titers. CONCLUSION: The test kit used in this study may not be adequate in older patients due to cross-reaction with C. pneumoniae titers. Further evaluation of C. trachomatis IgG titers as a marker in the study of ovarian cancer will require titers that are more specific than those we used. Although these titers may be useful as an immunologic screening marker in infertile patients, results should be interpreted with caution. A positive test may not be evidence of C. trachomatis infection and is not an indication for specific therapy. Successful use of some currently available C. trachomatis IgG titers in algorithms for infertility may be related to a patient's age.

Obesity and GnRH action. Report of a case with contribution by peripherally derived estrogens.

BACKGROUND: Gonadotropin-releasing hormone agonists (GnRH-a) are effective in reducing the pituitary release of gonadotropins, which, in turn, decrease ovarian steroidogenesis. The resulting menopausal state decreases the volume and vascular supply to uterine leiomyomas. Peripheral adipose tissue also contributes significantly to the circulatory estrogen pool, which is formed independent of pituitary function. As such, obesity may interfere with depot leuprolide acetate effects, allowing normal estrogen levels despite gonadotropin suppression. CASE: A premenopausal, morbidly obese woman was referred for treatment of menorrhagia and uterine leiomyomas. Despite administration of depot leuprolide, a GnRH-a, she continued to bleed heavily. Serum estradiol levels remained in the normal range, with suppression of follicle-stimulating hormone (FSH) levels. The desired hypoestrogenic effect from GnRH-a administration was thought to be negated by estradiol levels arising from peripherally derived conversion of adrenal androgens in adipose tissue. A GnRH stimulation test was performed to evaluate the responsiveness of the pituitary to the above therapy. While FSH was suppressed and unresponsive to stimulation, estradiol remained unchanged. CONCLUSION: Peripheral production of estrogen appears to be unaffected by leuprolide administration. Consideration should be given to the patient's body habitus when administering a GnRH suppressant. Morbidly obese patients possess an unlimited reservoir for peripheral estrogen synthesis.

Discontinuous Percoll gradient preparation for donor insemination: determinants for success.

The use of cryopreserved donor spermatozoa for insemination has become necessary to decrease the risk from sexually transmitted infectious diseases. Lower fecundity rates have been reported with this practice. Efforts have been applied to increase success, including identification of those sperm characteristics which correlate with increased fecundity. Data from in-vitro fertilization have revealed sperm morphology, motility and zona pellucida binding as important sperm parameters. Discontinuous Percoll gradient preparation yields a high concentration of motile spermatozoa. Using this preparation for thawed donor spermatozoa, we have identified post-preparation motility and progression as factors associated with increased fecundity. Consideration should be given to screening sperm donors with a freeze-thaw Percoll gradient preparation prior to acceptance into a donor bank.

A double-blind comparison of nafarelin and leuprolide acetate for down-regulation in IVF cycles.

OBJECTIVE: To compare nafarelin (NAF) with leuprolide acetate (LA) for pituitary down-regulation in IVF cycles. MATERIALS AND METHODS: Patients in a private IVF program who received both nasal spray and subcutaneous injections starting in the luteal phase prior to intended stimulation with any one route containing active drug in a randomized, prospective, double-blind study. Variables measured included the usual hormonal values as well as oocyte data, but not pregnancy rates, because of sample size and the heterogeneity of the study group. RESULTS: There were no differences between the two groups in the areas studied. CONCLUSION: Either NAF or LA can be used satisfactorily as an agent for pituitary down-regulation in IVF cycles.

Evaluating ovarian reserve: follicle stimulating hormone and oestradiol variability during cycle days 2-5.

A prospective measurement of follicle stimulating hormone (FSH) and oestradiol between cycle days 2 and 5 was conducted to investigate the intra- and inter-cycle variability in a healthy population of women with regular menstrual intervals. Daily serum samples were obtained from 44 women for a total of 66 cycles on cycle days 2, 3, 4 and 5. FSH concentrations were consistent on all cycle days measured. Oestradiol concentrations on cycle day 2 were not different from cycle day 3, but concentrations on cycle day 4 and cycle day 5 were statistically different from both cycle day 2 and cycle day 3 by analysis of variance (P < or = 0.05). Evaluation of functional ovarian reserved by cycle day 3 FSH measurement has become the standard in most assisted reproductive technology programmes. The recent change in FSH standardization coupled with the inflexibility of cycle day 3 testing has led to a re-evaluation of testing protocols. Cycle day 3 appears to have emerged as a dictum because most ovulation induction protocols are initiated on cycle day 3, 4 or 5. Flexibility of sampling day can be introduced as suggested by these results. The additional information ascertained from oestradiol testing as applied to evaluation of ovarian reserve warrants further investigation.

Intra-observer and inter-observer variability in scoring laparoscopic diagnosis of pelvic adhesions.

The objective of this study was to investigate intra-observer as well as inter-observer variability in the assessment of laparoscopic scoring of adhesive disease. Patients with suspected pelvic adhesions underwent a laparoscopic examination and surgical correction, using a standardized adhesion scoring system for severity as well as for extent of the adhesive process. An active agent or placebo was placed in the peritoneal cavity to discourage reformation of adhesions on a double-blind basis. A second laparoscopy was performed in 6-10 weeks and patients were re-scored. The videotapes were viewed and re-scored by the operator and four other gynaecological surgeons on two occasions, 3 months apart. Both adhesion severity and extent scores were lower following laparoscopic intervention. Reliability coefficients as defined by intra-class correlations were large indicating good reliability (0.778 and 0.758 for severity and extent respectively). Intra-observer (replication) variability was 12% of the total versus 19% for inter-observer variability of adhesion severity. These values were 15.4 and 22.3% of the total respectively, for adhesion extent. Individual observers tended to up-grade severity and minimize extent of adhesions when comparing the second with the first videotape views. The surgeon recorded greater adhesion score differences between the two procedures than the other observers. Though two physicians consistently had higher scores than two others, the intra-observer and interobserver variabilities were acceptable. Consultant review of high quality videotaped laparoscopic procedures is a valid method of independent assessment of operative findings.

Is paracervical block anesthesia for oocyte retrieval effective?

OBJECTIVE: To quantitate pain relief associated with paracervical local anesthesia during transvaginal ultrasound-guided collection. DESIGN: The study was a prospective, randomized, double-blinded, placebo-controlled, and no treatment-controlled investigation. Pain scores for vaginal pain associated with entry into the cul-de-sac and global assessment for the entire procedure were generated separately by patient and physician. Variables evaluated include duration of procedure, patient weight and age, total number of vaginal and ovarian "follicular" punctures, number of oocytes retrieved, and amount of IV medication. SETTING: A private IVF-ET program. PATIENTS: Women in an IVF-ET program who volunteered to join the study (n = 101). INTERVENTIONS: Local anesthesia as a paracervical block compared with placebo or no injection during transvaginal oocyte retrieval, with all patients receiving IV sedation. RESULTS: Both vaginal and global pain scores, whether patient or physician assessed were lower for paracervical block than placebo. Agreements between physician and patient assessments of pain scores were close. Duration of the procedure was correlated with pain score. In general, a placebo effect on pain perception compared with no injection was not seen. CONCLUSION: Paracervical local anesthesia compared with placebo injection was associated with lower pain scores for both vaginal puncture and global assessment of the oocyte retrieval process but was not significantly better than no injection for global evaluation.

Laparoscopic approach to definitive treatment of androgen insensitivity syndrome. A case report.

Androgen insensitivity syndrome is the most common form of male pseudohermaphroditism. This report describes a laparoscopic approach to diagnosis and gonadectomy in a patient with androgen insensitivity syndrome in whom the intraabdominal gonadal location was uncertain.

Effects of vasopressin administration during hysteroscopic surgery.

A study was performed to assess the effect of dilute vasopressin on intraoperative bleeding and intravasation of the medium during resectoscopic hysteroscopic surgery. Dilute vasopressin or placebo was injected into the cervical stroma at the commencement of resectoscopic endometrial ablation and/or submucous myomectomy in a prospective, computer-generated, double-blind, placebo study. The operator estimated the intraoperative bleeding. The inflow volume and outflow recovered volume of sorbitol, used as a distending medium, were recorded. Pressures were kept constant with a pump. Operating time was also recorded. In 64 women the mean inflow volume was 5,584 mL (range, 500-27,000), and the mean deficit (intravasation) was 311 mL (range, 0-2,100). The mean surgical time was 37.1 minutes (range, 11-120). The deficit volume was related to the duration of surgery (P = .001) and to total inflow volume (P = .001). Increased operating time and volume infused also increase intravasation. Multivariate analysis showed that patients receiving vasopressin had a 0.36 risk of intravasation (confidence limit, 0.14-0.91) as compared with the placebo. Vasopressin injected intracervically, in conjunction with resectoscopic intrauterine surgery, reduces but does not eliminate intravasation of the medium. It also decreases intraoperative bleeding.

Bilateral and unilateral gamete intrafallopian transfer (GIFT) are not equivalent therapies if unilateral GIFT is chosen to avoid one abnormal tube.

PURPOSE: The relative effectiveness of bilateral and unilateral gamete intrafallopian transfer (GIFT) was compared. Bilateral GIFT, where possible, was the preferred method of transfer and occurred in 328 patients. One hundred sixty-seven patients undergoing unilateral GIFT were placed into one of seven categories based on the indication for unilateral GIFT. Three categories included patients with either historical or laparoscopic evidence of unilateral tubal abnormalities, two categories included patients without tubal disease, and two categories contained patients in whom the physician could not choose between unilateral or bilateral GIFT. RESULTS: Results demonstrate that unilateral GIFT in patients with either historical or laparoscopic evidence of unilateral tubal disease had significantly lower pregnancy and implantation rates than patients undergoing bilateral GIFT or those undergoing unilateral GIFT without evidence of tubal disease (P < 0.01). CONCLUSION: The presence of unilateral tubal abnormalities predicts a lower likelihood of pregnancy in patients undergoing unilateral GIFT through the tube presumed to be normal.

Predicting success of gamete intrafallopian transfer.

OBJECTIVES: To examine seminal parameters predictive for success in a cycle of GIFT and to construct an algorithm using pertinent seminal data as well as easily obtained historical data to predict pregnancy and viable pregnancy rates. DESIGN: A retrospective study of 544 cycles in 376 couples. SETTING: A private IVF-ET and GIFT center. PATIENTS: Couples in a GIFT program with a mean of 53.6 months of infertility who had failed to conceive with other therapies. INTERVENTIONS: Gamete intrafallopian transfer. MAIN OUTCOME MEASURES: Pregnancy as a function of laboratory historical data with emphasis on seminal parameters. RESULTS: Motility was the only seminal parameter that was predictive. Success was correlated with the number of oocytes returned and inversely related to female age. An algorithm to predict pregnancy in a GIFT cycle as well as viable pregnancy was constructed. CONCLUSIONS: Motility is the only seminal parameter predictive for success in a GIFT cycle. An easily programmable algorithm can be constructed to help patient and physician decide on the appropriateness of GIFT for each couple.

The luteal phase after ovulation induction with human menopausal gonadotropin and one versus two doses of a gonadotropin-releasing hormone agonist.

OBJECTIVE: To use a GnRH agonist (GnRH-a) to induce ovulation after priming with exogenous hMG. DESIGN: Prospective, randomized double-blind protocol using one or two doses of intranasal nafarelin. SETTING: Office-based ovulation induction program. PATIENTS, INTERVENTIONS: Infertile women not conceiving after use of clomiphene citrate for at least 6 months who were given hMG and nafarelin. No luteal support was given. MAIN OUTCOME MEASURES: Serum concentrations of FSH, LH, E2, and P acutely and at 6 days after GnRH-a administration. Duration of the luteal phase was assessed. RESULTS: Ovulation with elevation of both FSH and LH was achieved. The two-dose regimen was more effective than one dose for sustained LH release. Luteal phase P values and luteal phase duration were both less than usually seen with gonadotropin hCG therapy in the absence of luteal phase support. CONCLUSIONS: Ovulation induction with GnRH-a after hMG priming produces unacceptable luteal phase cycles in the absence of hormonal support.

Microsurgical aspiration of sperm from the epididymis: a mobile program.

We report data from 25 microsurgical aspirations of the epididymis on 22 men. There were 14 men with congenital absence of the vas, 6 with failed vasoepididymostomy, 1 with adult cystic fibrosis and 1 with a childhood hernia repair. The specimens were used for assisted reproductive technologies, including in vitro fertilization and tubal embryo transfer. The protocol for aspiration, ovulation induction and sperm processing evolved during the course of these studies, and the patients were classified into 2 groups on the basis of methodology. Seventeen procedures were performed for the in-house in vitro fertilization team but 8 other procedures were done for nearby in vitro fertilization centers, and the final prepared sperm samples were transported as part of our mobile program. Group 1 patients underwent standard aspiration techniques, standard ovulation induction and sperm processing by wash and swim up. Among this group there were no fertilizations or pregnancies with 8 in-house and 2 transported specimens. Group 2 patients had leuprolide suppression before ovulation induction, direct intratubular aspiration and a complex sperm preparation, including pentoxifylline stimulation, mini-Percoll filtration and incubation with human follicular fluid. Among this group there were 2 fertilizations and 1 pregnancy with 9 in-house cases, and 3 fertilizations and 2 pregnancies with 6 transported specimens. These results suggest that a mobile program for microsurgical aspirations of sperm from the epididymis and in vitro fertilization or tubal embryo transfer is feasible within the framework of a strict protocol.