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Biomedical subjects

H Pinkas

Publications and source records attributed to H Pinkas.

At least 19 recordsLinked to original sources

Inclusion of standard and low-dose gonadotropin releasing hormone-analog (short protocol) in controlled ovarian hyperstimulation regimens in normogonadotropic patients aged 40-48 years who are undergoing in vitro fertilization.

We aimed to compare the efficiency of three controlled ovarian hyperstimulation protocols in achieving superovulation in normogonadotropic patients aged 40 years or more, who were undergoing in vitro fertilization (IVF) treatment. This was a prospective randomized clinical study, carried out in the Infertility and IVF Unit of an academic tertiary hospital. A total of 219 normogonadotropic patients (serum follicular stimulating hormone level < 15 mIU/ml) aged 40-48 years, with regular menstrual cycles, were randomly allocated to one of three short follicular protocols: menotropins only (group A), menotropins plus a mini-dose of gonadotropin releasing hormone (GnRH)-analog (600 microg/ day) (group B), or menotropins plus a standard dose (900 microg/day) of a GnRH-analog (group C). Those cycles that reached the stage of oocyte retrieval (67, 70 and 71 cycles, respectively) were analyzed. The mean daily dose of menotropins needed for ovarian stimulation was higher when GnRH-analog was used (groups B and C) (p < 0.02; ANOVA), although there was no significant difference in the time of human chorionic gonadotropin injection (average: cycle day 11). Peak estradiol levels (p < 0.02), number of oocytes retrieved (3.9, 5.4 and 5.5 oocytes/cycle, respectively, p < 0.02) and number of embryos transferred (1.6, 1.8 and 2.1 embryos/cycle, respectively, p < 0.05) were higher when GnRH-analog was included in the controlled ovarian hyperstimulation protocol. The IVF treatment resulted in 19 pregnancies (9.1% implantation rate), with a similar distribution among all three groups (11.9%, 8.6% and 7.0%). However, a higher miscarriage rate was noted in the menotropins-only group (67.5% vs. 33.3% and 40.0% of pregnancies). No differences were observed in any of the aforementioned variables between the mini-dose and standard dose GnRH-analog groups (groups B and C). In conclusion, controlled ovarian hyperstimulation before IVF treatment in normogonadotropic patients aged 40 years or more is more effective when a GnRH-analog (short protocol) is included in the treatment regimen. In this selected group of patients, reducing the daily dose of GnRH-analog does not improve the treatment results.

Adult↗

Is assisted hatching beneficial in patients with recurrent implantation failures?

PURPOSE: To assess the possible role of assisted hatching in patients with recurrent implantation failure during IVF cycles. DESIGN: Prospective randomized study. SETTING: IVF unit of an academic medical center. PATIENTS: Women who underwent IVF after at least three failed IVF-ET attempts. INTERVENTIONS: Patients were prospectively randomized to undergo assisted hatching of their embryos prior to their replacement by mechanical partial zona dissection. RESULTS: The study (assisted hatching) and control groups included 104 and 103 patients, respectively. There were no significant between-group differences in patient age, cause of infertility, mean number of previous IVF trials, number of oocytes retrieved, fertilization rate, or number of embryos transferred. No difference in pregnancy rate was noted on comparison of the whole study group, to the whole control group (21% and 27%, respectively). However, when the results were re-analyzed by age groups, assisted hatching was found to be harmful in the youngest group (< 34 years), significantly decreasing pregnancy rates (15% vs 35%, p < 0.05). CONCLUSION: Repeated implantation failure alone is not an indication for assisted hatching. Although assisted hatching appears to be effective in a selected group of older patients, in younger patients it may further hamper implantation and should be avoided.

Adult↗

Gonadotropin stimulation following GnRH-a priming for poor responders in in vitro fertilization-embryo transfer programs.

The effect of gonadotropin-releasing hormone agonist (GnRH-a) administration before gonadotropin superovulation on the stimulation characteristics of poor responder patients was assessed in an in vitro fertilization (IVF) program. Thirty consecutive patients who had exhibited low ovarian response (fewer than four retrieved oocytes) in at least two previous IVF cycles (control cycles, n = 60), were eligible for the study. GnRH-a (nafarelin) was administered daily for 7-10 days from the mid-luteal phase of the previous cycle until the first day of menstruation. Menotropin treatment was commenced on cycle day 3 (with no additional GnRH-a) (study cycles, n = 39). A significantly higher number of oocytes was retrieved (p < 0.0002) and a higher number of embryos transferred (p < 0.003) in the study cycles than in the control cycles. No cases of premature luteinizing hormone surge were recorded. Pregnancy rates per embryo transfer and per cycle were 10.4% and 7.7% for the study cycles and 2.8% and 1.6% for the control cycles, respectively. GnRH-a, administered prior to gonadotropin treatment, should be an additional option of ovulation induction protocol for poor responders in IVF programs.

Administration, Intranasal↗

Doppler parameters of uterine and ovarian stromal blood flow in women with polycystic ovary syndrome and normally ovulating women undergoing controlled ovarian stimulation.

OBJECTIVE: To test the hypothesis that the increased ovarian sensitivity to gonadotropins observed in women with polycystic ovary syndrome (PCOS) may be due to changes in ovarian stromal blood flow in these patients. DESIGN: Uterine and ovarian stromal arterial blood flow (with transvaginal color Doppler ultrasound) were measured in ten women with PCOS and 12 normo-ovulatory women (control group), undergoing gonadotropin stimulation before in vitro fertilization. METHODS: A careful ovarian stimulation strategy was adopted for the study group in order to avoid ovarian hyperstimulation syndrome and achieve an ovarian response which was comparable to that of the control group. Resistance and pulsatility indices (RI and PI) of the uterine and ovarian stromal arteries were calculated before the onset of gonadotropin treatment, on cycle day 5 (after commencing treatment), day of human chorionic gonadotropin injection, day of ovum pick-up as well as on the day of embryo transfer, and 7 and 12 days later. RESULTS: No significant differences were found in RI and PI between the study and control groups throughout the treatment cycle. CONCLUSIONS: It seems that polycystic ovaries do not bear an inherent disturbance in blood flow dynamics of the uterine and ovarian arteries, as measured by color Doppler, which would explain the increased sensitivity of polycystic ovaries to stimulation with gonadotropins.

Adult↗

Treatment variables in relation to oocyte maturation: lessons from a clinical micromanipulation-assisted in vitro fertilization program.

OBJECTIVE: In an effort to understand the mechanism underlying the improved pregnancy rate observed in IVF cycles when gonadotropin-releasing hormone analogues (GnRH-a) are applied, we investigated a possible relationship between treatment variables and oocyte nuclear maturity. DESIGN: Nuclear maturity was retrospectively assessed in cumulus-free, denuded oocytes, obtained from women undergoing micromanipulation-assisted IVF treatment following controlled ovarian hyperstimulation with GnRH-a and menotropins. SETTING: The setting was the infertility and IVF unit of a tertiary academic medical center. PARTICIPANTS: Two hundred twenty-one patients underwent 435 treatment cycles. MAIN OUTCOME MEASURE: This was the proportion of germinal vesicle-intact immature (GVII) oocytes. RESULTS: One hundred fifty-four of the 3520 oocytes studied (4.4%) were in the GVII stage. These oocytes were found in 66 of the treatment cycles (15.2%) and in 54 of the patients (24.4%). Cycles in which GVII oocytes were detected did not differ from those in which all the aspirated oocytes were mature in the following respects: patient age, type and duration of infertility, controlled ovarian hyperstimulation protocol and time of ovum pickup. However, the GVII group was characterized by a significantly higher peak estradiol level, as well as a higher number of mature follicles visualized sonographically (diameter, > 14 mm) and oocytes retrieved. CONCLUSIONS: Comparing the present findings with previously published data, it appears that the inclusion of GnRH-a in the stimulation regimen is associated with a lower proportion of immature oocytes. A higher occurrence of oocyte-nuclear immaturity is apparently associated with a significantly better ovarian response to stimulation. The high incidence of immature oocytes observed in patients with normospermic partners and low fertilization rates in previous cycles may suggest that the fertilization failure in some of these cases is due to oocyte, rather than sperm, dysfunction.

Adult↗

Esophagitis associated with the use of alendronate.

BACKGROUND: Alendronate, an aminobisphosphonate and a selective inhibitor of osteoclast-mediated bone resorption, is used to treat osteoporosis in postmenopausal women and Paget's disease of bone. Aminobiphosphonates can irritate the upper gastrointestinal mucosa. METHODS: We describe three patients who had severe esophagitis shortly after starting to take alendronate and also analyze adverse esophageal effects reported to Merck, the manufacturer, through postmarketing surveillance. RESULTS: As of March 5, 1996, alendronate had been prescribed for an estimated 475,000 patients worldwide, and 1213 reports of adverse effects had been received. A total of 199 patients had adverse effects related to the esophagus; in 51 of these patients (26 percent), including the 3 we describe in case reports, adverse effects were categorized as serious or severe. Thirty-two patients (16 percent) were hospitalized, and two were temporarily disabled. Endoscopic findings generally indicated chemical esophagitis, with erosions or ulcerations and exudative inflammation accompanied by thickening of the esophageal wall. Bleeding was rare, and stomach or duodenal involvement unusual. In patients for whom adequate information was available, esophagitis seemed to be associated with swallowing alendronate with little or no water, lying down during or after ingestion of the tablet, lying down during or after ingestion of the tablet, continuing to take alendronate after the onset of symptoms, and having preexisting esophageal disorders. CONCLUSIONS: Alendronate can cause chemical esophagitis, including severe ulcerations, in some patients. Recommendations to reduce the risk of esophagitis include swallowing alendronate with 180 to 240 ml (6 to 8 oz) of water on arising in the morning, remaining upright for at least 30 minutes after swallowing the tablet and until the first food of the day has been ingested, and discontinuing the drug promptly if esophageal symptoms develop.

Aged↗

The initial flare-up induced by gonadotropin releasing hormone agonist may serve as a predictor of ovarian response in the current IVF-ET treatment cycle in normogonadotropic women aged 40-48 years.

OBJECTIVE: Our purpose was to assess the potential role of the baseline hormone profile in combination with the initial pattern of response to gonadotropin releasing hormone (GnRH) analogue in predicting ovarian function and hence reproductive outcome in normogonadotropic patients aged 40 years or older undergoing IVF treatment. PATIENTS AND METHODS: A retrospective analysis of 394 controlled ovarian hyperstimulation (COH) cycles that reached the stage of oocyte retrieval was conducted. The study included 163 normogonadotropic (serum FSH < or = 15 IUIL) patients aged between 40 and 48 years who had regular menstrual cycles. Superovulation was achieved using menotropins in combination with GnRH analog (short protocol, beginning on menstrual day 2). The ovarian response was monitored on the third cycle day, the day following the first GnRH analogue administration. RESULTS: Cycle distribution by patient age was 175 (44.4%), 122 (30.9%), and 97 (24.7%), while the patient distribution was 85 (52.2%), 48 (29.5%), and 30 (18.3%) for age groups 40-41, 42-43, and 44-48 years, respectively. The mean total dose of menotropins needed for optimal COH was 1787 IU (range, 600-6000 IU). This dose increased with age, while the yield of oocytes and embryos declined (P < 0.05; ANOVA). A positive correlation was demonstrated between the E2 level on day 3 (GnRH analogue flare effect) and the outcome of the treatment cycle (number of oocytes and embryos). Using multiple stepwise regression analysis, it was demonstrated that the initial (day 3) serum E2 levels, combined with baseline FSH levels, patients's age and body mass index enabled early prediction of the ovarian response in the current IVF-ET treatment cycle (oocytes = 8.2 - 0.18 x Age + 0.17 x BMI - 0.12 x FSH + 0.0042 x E2). CONCLUSIONS: Multiple-parameter analysis demonstrated that the use of the initial E2 response to GnRH analogue stimulation combined with basic clinical data may assist in the prediction of ovarian function and hence the reproductive outcome in normogonadotropic IVF patients aged 40 years or older. This may serve as a clinical tool for improving patient selection and treatment outcome in IVF-ET.

Adult↗

Intranasal nafarelin versus buserelin (short protocol) for controlled ovarian hyperstimulation before in vitro fertilization: a prospective clinical trial.

The aim of this study was to compare the effect of nafarelin acetate with that of buserelin acetate nasal spray, when administered in a 'short' protocol, as an adjunct to human menopausal gonadotropin (hMG) for controlled ovarian hyperstimulation before in vitro fertilization (IVF). Twenty-two IVF subjects were randomly recruited. Each underwent two consecutive treatment cycles; one with buserelin (900 micrograms/day) and another with nafarelin (400 micrograms/day). The treatment protocol included transnasal gonadotropin-releasing hormone (GnRH) analog from the second cycle day and hMG from the fourth day of the cycle. The buserelin and nafarelin cycles did not differ significantly in the following parameters: baseline hormone profile, duration of GnRH analog treatment, mean hMG dose required, peak estradiol levels, number of preovulatory follicles, number of aspirated oocytes, fertilization rate and number of transferred or frozen embryos. No side-effects or cancellations of treatment were recorded. The average dose required was lower for nafarelin and, because this analog was given only twice a day, it was more convenient to administer. These findings suggest that nafarelin is as effective as buserelin (when administered in a "short' protocol) in achieving controlled ovarian hyperstimulation. It even offers advantages over buserelin with respect to the total dose required (which probably reflects its relatively high potency) and the subjects' compliance.

Administration, Intranasal↗

Augmentation of low ovarian response to superovulation before in vitro fertilization following priming with contraceptive pills.

Poor ovarian response to superovulation treatment is observed in a certain group of patients, the so-called 'low responders'. Despite the evolution of sophisticated controlled ovarian hyperstimulation (COH) regimens prior to the in vitro fertilization (IVF), the ideal stimulation protocol for the low responder has yet to be formulated. The objective of this study was to assess the effect of oral contraceptive pills (OCP), administered before the initiation of superovulation, on ovarian response and IVF treatment results in patients with previous 'low response' to exogenous gonadotropin stimulation. The study group comprised 42 patients who had exhibited poor ovarian response to standard superovulation protocols in at least two previous consecutive treatment attempts. Contraceptive pills were administered for 28-42 days and were immediately followed by menotropin treatment. The study group (n=50 cycles) was compared with the control group consisting of previous cycles (n=88) of the same women. Significant differences were noted in peak estradiol levels (983 +/- 739 vs. 517 +/- 249 pg/ml; P <0.01, paired Student's t test) and number of pre-ovulatory follicles between the study and the control groups. Thirty-three of the cycles (66%) reached the stage of ovum pick-up, compared with 22 (25%) of the previous IVF cycles in these women. The mean number of oocytes retrieved was 6.1 +/- 3.0 and 2.4 +/- 1.3 in the study and control groups, respectively (P <0.01; paired Student's t test). Embryo transfer (ET) was performed in 62% of the treatment cycles and resulted in five clinical pregnancies (16.1% per ET). No pregnancies were recorded in the control group. This study demonstrates the beneficial effect of OCP given prior to IVF treatment, and provides an efficient treatment modality for women who consistently respond poorly to standard COH protocols.

Adult↗

Superovulation before IVF by recombinant versus urinary human FSH (combined with a long GnRH analog protocol): a comparative study.

PURPOSE: Gonal-F (Serono, Aubonne, Switzerland) is a recombinant human follicle stimulating hormone (FSH) synthesized in vitro by cells into which genes encoding for FSH subunits have been inserted. This preparation exhibits physiochemical, immunological, and pharmacological properties that bear great similarity to those of native human FSH. It has a high specific activity and can be administered subcutaneously. To compare the efficacy and safety of Gonal-F with those of urinary human FSH (Metrodin; Serono) in achieving superovulation for IVF purposes in a prospective, randomized study. METHODS: Twenty infertile patients (normo-ovulatory healthy women) were recruited for the study and allocated at random to the Gonal-F or Metrodin groups. The treatment protocol consisted of pituitary down regulation by GnRH analog (Buserelin; Hoechst, Frankfurt, Germany) employing the "long" protocol initiated at the mid-luteal phase (900 micrograms/day, intranasal administration). Gonal-F (SC) or Metrodin (IM) was injected daily (225 IU/day) starting on cycle day 3. Dose adjustment was performed, when necessary, from cycle day 7. RESULTS: Of the 20 cycles analyzed, none was canceled due to poor response. No cases of adverse effects (including local intolerance) or ovarian hyperstimulation syndrome were recorded in either group. They did not differ significantly in the following treatment-dependent variables: hormone profile, duration of FSH treatment, total FSH dose required to achieve follicular maturation, and the number of oocytes retrieved, fertilized, and replaced. CONCLUSIONS: These preliminary data concur with previous studies in demonstrating that Gonal-F is as effective and safe as Metrodin (when given in combination with a "long" protocol of GnRH analog) in inducing controlled ovarian hyperstimulation for IVF purposes. Its mode of administration (SC instead of IM) offers an additional advantage over the urinary human FSH.

Adolescent↗

Assisted hatching by partial zona dissection of human pre-embryos in patients with recurrent implantation failure after in vitro fertilization.

OBJECTIVE: To examine the potential of the partial zona dissection technique to promote successful implantation by assisting embryo hatching after IVF. DESIGN: The study and the control group included 72 and 82 patients, respectively, each had undergone at least three failed IVF-ET attempts. Assisted hatching was performed on four- to six-cell stage embryos by creating a slit in the zona pellucida using the partial zona dissection technique. After 90 minutes incubation (5% CO2, 37 degrees C), the embryos were transferred to the uterus. SETTING: Infertility and IVF Unit of an academic tertiary referral medical center. RESULTS: In the assisted hatching group, 230 micromanipulated embryos were replaced (3 or 4 treated embryos per patient) compared with 295 nonmanipulated embryos in the control group. Clinical pregnancy rates (PRs) were similar in the assisted hatching and control groups (n = 15; 20.8% and n = 12; 14.6%, respectively). However, the contribution of assisted hatching by partial zona dissection to successful implantation was related to the patients's age: patients older than 38 years showed a markedly higher PR after assisted hatching: 23.9% in the study group compared with only 7% of the controls. CONCLUSIONS: These results demonstrate that assisted hatching by partial zona dissection is a quick and efficient method that does not induce any visible damage to the embryos replaced. In a selected group of patients (aged over 38 years, who have failed to conceive in at least three previous IVF attempts) it significantly increases the chances for pregnancy after ET.

Adult↗

Prolonged evaluation of epinephrine and normal saline solution injections in an acute ulcer model with a single bleeding artery.

BACKGROUND: Animal studies of epinephrine or normal saline solution injection for bleeding ulcers do not consistently demonstrate local tamponade effect. METHODS: We studied the change of bleeding rates of 28 acute gastric ulcers with a single bleeding artery in 10 dogs. Four injections of 1 mL epinephrine 1:10000 at 1 mm from the spurting artery (n = 7) were compared to four injections of normal saline solution 1 to 5 mL (n = 12) and to four dry needle sticks (n = 9). Bleeding rates were measured at initial arterial incision and at minutes 1, 5, 10, 15, 20, 25, and 30 after treatment. RESULT: Reductions in early blood loss to 24.3% +/- .05 of baseline occurred with saline solution, to 17.7% +/- .03 with epinephrine, and to 66.0% +/- 1.8 in controls (p < .05 for epinephrine and saline solution vs control). A tendency for saline solution injected ulcers to resume bleeding was identified, with late blood loss increasing to 26.9% +/- .05 of baseline, (saline solution vs control) compared to 7.7% +/- .02 in epinephrine injected ulcers (p < .05 vs control). CONCLUSIONS: The early acute hemostatic effect of injection therapy depends on local tamponade. The prolonged hemostatic effect is a combination of tamponade and vasoconstriction, with advantage of epinephrine over saline solution.

Animals↗

Endoscopic basket impaction.

Endoscopic Retrograde Cholangiopancreatography (ERCP) is an indispensable tool for imaging the pancreatico-biliary tree, and in treating diseases of the pancreatic and biliary systems. ERCP plays a primary role in the management of choledocholithiasis, both in diagnosis and treatment. Complications occur infrequently and can usually be treated nonoperatively. An unusual complication of ERCP and an impacted stone retrieval basket are presented and discussed along with review of the medical literature.

Catheterization↗

Massive GI hemorrhage from an ileal duplication cyst in an adult.

We describe an unusual case of a 32-yr-old man who presented with massive GI hemorrhage as an initial manifestation of an ileal duplication cyst. The lesion was first revealed by visceral angiography during investigation of the bleeding source. At laparotomy, a large ileal duplication containing full-thickness gastric-type mucosa was identified. Ulceration of the ileal mucosa adjacent to the communicating orifice was found to be the source of bleeding. Duplications of the alimentary tract are rare congenital malformations. Patients usually present in infancy and childhood, although delayed complications can present in adulthood. This entity should be considered among other lesions that can cause massive GI hemorrhage not diagnosable by endoscopy.

Adult↗

The role of ERCP in patients after laparoscopic cholecystectomy.

OBJECTIVES: The goal of this study was to evaluate the feasibility of endoscopic management of complications encountered in patients undergoing laparoscopic cholecystectomy. Special attention was given to establishing the optimal timing, success rate, and complications of diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP) after laparoscopic cholecystectomy. METHODS: Fifty-six consecutive patients referred from two major medical centers were evaluated with ERCP after laparoscopic cholecystectomy. The patient population included 22 men and 34 women 16-87 yr of age. Indications included common bile duct stones seen on operative cholangiography or ultrasound, persistently elevated liver enzymes and abdominal pain, evidence of biliary injury, and other, All endoscopic procedures were carried out by experienced endoscopists using standard ERCP techniques and equipment. Endoscopic papillotomy was performed with 2- to 2.5-cm cutting wire papillotomes and all biliary stones were removed with 8.5- to 14-mm balloons. Small biliary leaks were first treated with 3-7 days of nasobiliary drainage, and if persistent with 10-Fr internal stents for 1 month. One patient with a biliary stricture was dilated with placement of progressively larger biliary stents over 9-month period. RESULTS: ERCP was performed within 6 h to 2 yr after laparoscopic cholecystectomy (LC). In 12 patients, it was performed within the first 24 h after LC. A cholangiogram was obtained in all patients. No complications were encountered. Thirty patients underwent therapeutic endoscopy. Common bile duct stones were found and were successfully removed from 23 patients. One patient required an emergent ERCP and sphincterotomy for gallstone pancreatitis 3 days after LC. Fourteen patients had common bile duct injuries, cystic duct stump leaks, or leakage from ducts of Luschka (one patient). All leaks were successfully treated with temporary stenting. Six patients with bile duct transection or complete obstruction by clips required surgical therapy. One patient with a common bile duct stricture was managed with endoscopic stents alone. Two patients had unsuspected malignancies, one each with ampullary and pancreatic carcinoma. Fourteen patients had a normal ERCP. CONCLUSIONS: Diagnostic and therapeutic ERCP can be done within 24 h of LC with safety and a high degree of success. Delay in removal of CBD stones may lead to complications. Cystic duct stump leaks are easily corrected with nasobiliary drainage, and some post-LC strictures may be amenable to therapy with biliary stents. Finally, malignancy must be excluded in patients with unexplained recurrent symptoms.

Adolescent↗