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Biomedical subjects

J N Gutmann

Publications and source records attributed to J N Gutmann.

At least 19 recordsLinked to original sources

Laparoscopy in the "normal" infertile patient: a question revisited.

STUDY OBJECTIVE: To determine the prevalence of reproductive pathology in a group of infertile women thought to be at low risk for altered pelvic anatomy. DESIGN: Retrospective chart review and follow-up (Canadian Task Force classification II-2). SETTING: Academic-affiliated, private reproductive endocrinology practice. PATIENTS: One hundred infertile women. INTERVENTION: Diagnostic and/or therapeutic laparoscopy. MEASUREMENTS AND MAIN RESULTS: Of 100 patients with a negative reproductive work-up up to the point of laparoscopy, 68 had pathology of reproductive significance: intrinsic tubal disease 24, peritubal adhesive disease 34, and endometriosis 43, some in combination. Laparoscopy was especially helpful in establishing treatment protocols for older women, who were referred for assisted reproductive techniques earlier than otherwise might have been the case. Women conceived after hormone therapy and after operative intervention. Although the hysterosalpingogram was read as normal in all women, tubal disease was diagnosed laparoscopically, independent of endometriosis, in 27 patients, with 2 having complete obstruction. Endometriosis stage I-II was found in 22 patients, stage III in 13, and stage IV in 6. CONCLUSION: Even in women thought to be at low risk for significant pelvic pathology affecting reproduction, the yield was high. Although some pregnancies were achieved after operative intervention, frequently laparoscopy was helpful in making a decision to go to assisted reproductive technology, particularly when infertility had been of long duration and in older women. Frequently the degree of pathology was such that a full operating suite was necessary to provide adequate instrumentation and anesthesia for operative intervention, which would not have been the case with office laparoscopy.

Adult↗

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.

Adult↗

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.

Adult↗

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.

Adult↗

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.

Adnexal Diseases↗

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.

Adult↗

Endometriosis.

Explore the source record for details and available documents.

Adult↗

Reproductive potential after treatment for persistent ectopic pregnancy.

We examined the success rate and reproductive outcome of 50 patients who had been treated for persistent EP after initial unsuccessful salpingostomy. All who underwent salpingectomy had successful treatment of their persistent EP. One treatment failure occurred after MTX. Of 50 women, 32 (61.5%) attempted conception after treatment for persistent EP. The cumulative clinical pregnancy rate after treatment for persistent EP was 59% at 36 months. There was a significant association between clinical pregnancy rate after persistent EP and those with normal contralateral fallopian tubes (P < 0.005). The relative risk of having a clinical pregnancy among those who attempted conception was 2.3 for those having a normal contralateral fallopian tube compared with those with a contralateral fallopian tube with obvious pathology. Intrauterine pregnancy rates after treatment of persistent EP were similar to those reported for primary treatment of EP.

Adult↗

Evaluation of leuprolide acetate treatment on histopathology of uterine myomata.

OBJECTIVE: To determine if short-term, preoperative leuprolide acetate (LA) therapy alters the histologic appearance of uterine leiomyomata. DESIGN: Retrospective evaluation by a pathologist (who was blinded to patient history) of the histologic features of leiomyomata excised from 36 women, 12 who received preoperative LA and 24 age-matched controls. SETTING: Yale-New Haven Hospital, New Haven, Connecticut, from September 1989 to September 1990. MAIN OUTCOME MEASURE: The histologic specimens were evaluated for the presence of mitotic activity, cellular atypia, cellularity, and secondary changes including edema, fibrosis, calcification, hemorrhage, infarction, hyalinization, and vascular appearance. RESULTS: Of the 12 patients treated with LA, 10 (84%) demonstrated a reduction in uterine volume after 3 to 6 months of LA therapy. There was no difference in any of the histopathologic parameters evaluated between the LA-treated group and the untreated group. Exclusion of leiomyoma, which did not have a reduction in size during LA therapy, did not alter the analysis. Among patients treated with LA, those leiomyoma that did not respond to LA had a greater degree of hyalinization than those that responded. CONCLUSION: Reduction in uterine size by short-term LA therapy did not detectably alter histologic appearance of leiomyoma.

Adult↗

Dichloroacetic acid accelerates initial development of 2-cell murine embryos in vitro.

Preimplantation embryos up to the 8-cell stage of development use lactate and pyruvate but not glucose or Krebs cycle intermediates to support growth, development, and cleavage. The dominant effect of dichloroacetic acid (DCA) is the irreversible stimulation of pyruvate dehydrogenase (PDH) activity, thus accelerating the oxidative metabolism of pyruvate and lactate. To test the hypothesis that early induction of oxidative metabolism in 2-cell murine embryos accelerates preimplantation embryo cleavage rates, female B6C3F1 mice at 6 to 8 weeks of age were superovulated with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) and mated. All 2-cell stage embryos were randomly assigned to culture media with or without 130 micrograms/mL DCA. The developmental stage of all embryos was then noted every 24 hours for a total of 72 hours. Chi-square analysis and the method of average rank sum were used to compare the distribution of embryos at each observation point. At 24 hours, DCA-exposed embryos had achieved an advanced stage of growth and development relative to controls (average rank sum, P = .026; chi-square distribution, P = .047). Subsequently, at 48 and 72 hours, neither the average rank sum nor the chi-square distribution was different. Our data suggest that DCA accelerates early growth and development of murine embryos before implantation, possibly through the early induction of oxidative metabolism.

Animals↗

Human granulosa-luteal cells secrete parathyroid hormone-related protein in vivo and in vitro.

The presence of mRNA transcripts and/or immunoreactivity for PTH-related protein (PTHrP) in several normal mammalian tissues suggests a possible paracrine or autocrine role for this hormone. Since immunohistochemical studies of human ovary demonstrate the presence PTHrP immunoreactivity in this tissue, we wondered if ovarian follicular fluid (OVFF) might contain PTHrP. We retrospectively analyzed 28 OVFF samples obtained at ova harvest in 21 women undergoing in vitro fertilization. Fourteen samples contained significant adenylate cyclase-stimulating activity in a PTHrP-sensitive bioassay. In a subsequent prospective analysis, 41 of 45 freshly obtained OVFF samples demonstrated significant activity. This bioactivity was completely neutralized by antisera to PTHrP, but was unaffected by antisera to PTH. Fifteen OVFF samples were also analyzed in a sensitive 2-site immunoradiometric assay for PTHrP, and all 15 demonstrated significant levels of the hormone. The PTHrP levels did not correlate with the presence of an ovum in the follicle or with follicular fluid calcium. Short term (24- to 48-h) cultures of granulosa-luteal cells established from 5 OVFF samples demonstrated constitutive secretion of PTHrP using the immunoradiometric assay. Neither progesterone nor estrogen affected basal secretion. RNase protection analysis of cellular RNA prepared from cultured granulosa-luteal cells demonstrated the presence of mRNA for PTHrP in these cells. We conclude that 1) human OVFF obtained after stimulation with FSH and LH contain high concentrations of PTHrP; and 2) the granulosa-luteal cell is capable of secreting PTHrP both in vivo and in vitro.

Biological Assay↗

Comparison of persistent ectopic pregnancy after laparoscopic salpingostomy versus salpingostomy at laparotomy for ectopic pregnancy.

OBJECTIVE: To compare persistent ectopic pregnancy after laparoscopic salpingostomy versus salpingostomy at laparotomy for the treatment of intact ampullary ectopic pregnancy. METHODS: We reviewed the medical records of 157 patients who had undergone salpingostomy for intact ampullary ectopic pregnancy at Yale-New Haven Hospital between September 1, 1986 and August 31, 1991. One hundred three women had laparoscopic salpingostomy and 54 had salpingostomy at laparotomy. RESULTS: Sixteen of 103 women (15.5%) undergoing laparoscopic salpingostomy were treated for persistent ectopic pregnancy, in contrast to one of 54 women (1.8%) who had salpingostomy by laparotomy. The adjusted odds ratio for persistent ectopic pregnancy after laparoscopic salpingostomy versus salpingostomy at laparotomy for an intact ampullary ectopic pregnancy was 8.4, with 95% confidence interval 1.1-62 (P < .02). Stepwise logistic regression demonstrated that a laparoscopic approach to salpingostomy (P < .05), smaller ectopic size (P < .01), and fewer days of amenorrhea (P < .05) predicted persistent ectopic pregnancy. CONCLUSION: Persistent ectopic pregnancy is more likely after laparoscopic salpingostomy than after salpingostomy at laparotomy for intact ampullary ectopic pregnancy.

Cohort Studies↗

Luteinizing response to human chorionic gonadotropin does not predict outcome in gonadotropin releasing hormone agonist-suppressed/human menopausal gonadotropin-stimulated in vitro fertilization (IVF) cycles.

OBJECTIVE: The purpose of this study was to determine if early luteinizing potential in gonadotropin releasing hormone agonist (GnRH-a)-suppressed/human menopausal gonadotropin (hMG)-stimulated IVF cycles is predictive of cycle outcome. DESIGN, PATIENTS: The study was a prospective evaluation of 41 women beginning a GnRH-a-suppressed/hMG-stimulated IVF cycle. SETTING: The in vitro fertilization program of a tertiary care institution was the study setting. MAIN OUTCOME MEASURES: The main outcome measures were (1) estradiol (E2) and progesterone (P) levels on the day of human chorionic gonadotropin (hCG) administration and the following day and (2) the ovarian response to ovulation induction and clinical outcome. RESULTS: Ten of the 41 women achieved a clinical pregnancy (24.4%). There was no significant difference in progesterone (P) levels on the day of or the day following hCG administration between the pregnant and the nonpregnant groups. Both groups exhibited a significant rise in P level in response to hCG. There was no significant difference in E2 levels on the day of hCG between the two groups. The serum E2 did not rise significantly in response to hCG in either group. Patients who became pregnant had significantly more oocytes retrieved, fertilized, cleaved, and transferred. CONCLUSIONS: Clinical response and outcome in GnRH-a-suppressed/hMG-stimulated IVF cycles are not predicted by early luteinizing potential as indicated by the response of E2 or P to hCG.

Adult↗

The role of office hysteroscopy in in vitro fertilization.

Twenty-eight patients participated prospectively in a study to evaluate the impact of hysteroscopically detected uterine and cervical anomalies on the success rate of ET in an IVF-ET program. All participants had a normal intrauterine cavity by standard HSG. All the patients had a diagnostic office hysteroscopy under paracervical block before commencing COH. Because our IVF program does not include hysteroscopy as a requirement before undergoing IVF and because the significance of mild intrauterine abnormalities is not yet known, the hysteroscopic findings were not relayed to the personnel involved in the IVF-ET procedure. Sixteen patients (group I) had a normal hysteroscopic evaluation. Twelve patients (group II) had abnormal hysteroscopic findings including small uterine septa, small submucous fibroids, uterine hypoplasia and cervical ridges. Although no difference in patients or cycle characteristics was present, there was a significant difference in the clinical PR between patients in groups I and II. In conclusion, in an IVF-ET program patients with normal hysterography but abnormal hysteroscopic findings had a significantly lower clinical PR, demonstrating the importance of performing hysteroscopy before IVF-ET.

Adult↗

Nafarelin versus leuprolide in ovulation induction for in vitro fertilization: a randomized clinical trial.

Gonadotropin-releasing hormone agonists vary in structure and route of administration. We performed this study to compare patient response to intranasal nafarelin acetate versus subcutaneous leuprolide acetate as adjuncts to ovulation induction for in vitro fertilization (IVF). Forty-two patients entering their first cycle of IVF were randomized to receive either nafarelin acetate or leuprolide acetate. Patient characteristics in the two groups did not differ significantly, nor did cycle cancellation rates or outcome. There was no significant difference in patient response as indicated by follicular phase serum levels of estradiol (E2), FSH, or LH, luteal phase E2, and progesterone. Luteal phase progesterone-dependent endometrial protein was significantly lower in those taking nafarelin acetate, though it remained in the normal range. However, those receiving nafarelin acetate required significantly less human menopausal gonadotropin (hMG) and had significantly more embryos frozen for later transfer than those receiving leuprolide acetate. Intranasal nafarelin acetate can be used successfully in ovulation induction regimens that include GnRH agonists. The use of nafarelin acetate may decrease a patient's hMG requirement and increase the number of frozen embryos available for later transfer as compared with leuprolide acetate. Further studies are needed to optimize the dosing regimen.

Administration, Intranasal↗

Persistent ectopic pregnancy following laparoscopic linear salpingostomy.

As the surgical approach for ectopic pregnancies evolves from radical to conservative procedures, the potential hazard of persistent ectopic pregnancy has become increasingly pertinent. From September 1, 1986 to August 31, 1989, 11 women with persistent ectopic pregnancy after laparoscopic salpingostomy were diagnosed and treated at Yale-New Haven Hospital. Persistent ectopic pregnancy was suspected in nine cases because of symptoms and in two because of plateauing beta-hCG titers. Ten of 11 patients underwent repeat surgery. Eight had partial or complete salpingectomy of the involved ipsilateral tube, two had repeat salpingostomies, and one was treated with methotrexate. When the 11 women with persistent ectopic pregnancies were compared with 70 patients treated successfully by laparoscopic salpingostomy using multivariate stepwise logistic regression, smaller size of the ectopic (P less than .01) and fewer days of amenorrhea (P less than .05) predicted persistent ectopic pregnancy after laparoscopic salpingostomy. Based upon our experience, we believe that earlier-treated ectopic pregnancies (ie, fewer than 42 days of amenorrhea) and/or smaller ectopics (ie, 2.0 cm or less in diameter) require treatment with particular caution and close postoperative surveillance.

Chorionic Gonadotropin↗