Biomedical subjects
Publications and source records attributed to A Hershlag.
Pregnancy rates per cycle reported from different in vitro fertilization-embryo transfer programs vary widely. While several programs have reported constant pregnancy rates per cycle, others report declining pregnancy rates. Selection biases at the point of entry and between cycles are discussed as possible explanations of these discrepancies.
OBJECTIVE: To evaluate the variability of follicle stimulating hormone (FSH) and estradiol (E2) results from different laboratories. DESIGN: Prospective analyses of sera separated and frozen, obtained from 15 female patients in the follicular phase. All kits used for radioimmunoassay (RIA) for FSH were from the Second International Reference Preparation (IRP). Four different kits were used for FSH and three for E2. SETTING: Sera obtained from each patient were separated into five test tubes and frozen. Analysis of all samples was done on the same day in each one of five participating hospital-based RIA laboratories (North Shore, Cornell, Yale, Mount Sinai, and Norfolk). PARTICIPANTS: Fifteen consecutive patients from the assisted reproductive technology program at North Shore University Hospital participated in the study. MAIN OUTCOME MEASURES: After FSH and E2 levels were tabulated for each laboratory, mean levels were calculated. RESULTS: Using the Bonferroni adjusted pairwise multiple comparisons analysis, significant differences were found between three groups of laboratories within the FSH results and three different groups within the E2 results. CONCLUSIONS: [1] Different results may be obtained on the same sera for FSH and E2 at different laboratories; [2] for FSH, even though the same IRP is used, different results are reached; [3] for E2, even when the same kits are used, results may be significantly different. These results suggest that specific FSH and E2 levels used to predict chances for achieving a viable pregnancy through in vitro fertilization should be interpreted with caution across institutions.
The potential role of interleukin-1 in postoperative adhesion formation was examined. Cecal abrasion gave a consistently higher adhesion score when compared with sham laparotomy, on the basis of adhesion number, density, and vascularity, and so was chosen for use in further studies. The extent of serosal bleeding during cecal abrasion did not affect adhesion scores. Intraperitoneal injection of 10 micrograms murine recombinant interleukin-1 alpha in cecally abraded animals on the day of surgery and on the following 4 days resulted in a significant increase in adhesion scores when compared with those of cecally abraded animals injected with vehicle alone. Adhesions enhanced with murine recombinant interleukin-1 alpha, which were thicker and more vascular, were equivalently enhanced at doses from 10 to 10,000 ng, implying maximal response over that range. Rats not operated on and receiving recombinant interleukin-1 alpha 2 weeks after injury had increased adhesion formation. These results demonstrate that interleukin-1 alpha may be an important short-term mediator of postsurgical adhesion formation.
Failure of the normal ejaculatory mechanism may lead to retrograde ejaculation. This occurs most commonly as a result of transurethral prostatectomy, retroperitoneal lymph-node dissection and diabetic neuropathy. The diagnosis is based on the absence of sperm in the antegrade ejaculate and the presence of sperm in the post-masturbatory urine. If pharmacologic attempts to restore antegrade ejaculation fail, sperm recovery from the urine and intrauterine insemination are usually indicated. Surgical alternatives are discussed.
Lysis of adhesions improves pregnancy rates. Results of laparoscopic lysis are not different from those of laparotomy. Since laparoscopy is more convenient to the patient, less expensive, saves hospital beds, and involves low morbidity, it should be the preferred surgical approach to the diagnosis and treatment of pelvic adhesions whenever possible. The use of a sharp dissection combined with electrocautery seems, at this time, to be equally effective to the use of lasers of different kinds. Adjuvants presently available, especially Hyskon or INTERCEED, have an added benefit to surgery alone. Even with the best surgical technique, adhesions tend to re-form. Although SLL will identify the extent of adhesion re-formation, the therapeutic advantage of lysing re-formed adhesions is yet to be proved.
OBJECTIVE: To evaluate the efficacy of in vitro fertilization and embryo transfer (IVF-ET). DESIGN: Two different models for pregnancy rates in IVF-ET have been developed: a beta-geometric model and a split population model. SETTINGS: All IVF cycles were performed at the Yale University School of Medicine in New Haven, Connecticut. PATIENTS, PARTICIPANTS: All patients undergoing 1,257 IVF-ET cycles performed between the years 1983 through 1987. INTERVENTIONS: None. MAIN OUTCOME MEASURE: The probability of achieving a viable pregnancy per cycle. RESULTS: Because both models provide excellent explanations for our data distribution, the decline in the conditional probability of achieving pregnancy after a given number of unsuccessful cycles may be inferred. CONCLUSIONS: These findings question the justification of continuing IVF-ET treatment beyond some threshold number of cycles.
In order to examine the ability of salpingoscopy to diagnose intratubal pathology, 32 fallopian tubes were evaluated salpingoscopically and histologically. Both flexible and rigid salpingoscopes were used, and observations were documented by intratubal photography. Salpingoscopic criteria were established and each criterion assigned a numerical value. Each tube was evaluated for patency, mucosal fold architecture, erythema, adhesions, and dilatation. Based on these criteria, tubes were graded as normal or as abnormal with mild, moderate, or severe changes. Histologically, each tube was evaluated for patency, epithelial changes, vascularity, dilatation, adhesions, and active inflammation. Six tubes with significant histologic findings and two histologically normal fallopian tubes were also examined by transmission electron microscopy. In five discordant cases, histology revealed epithelial and stromal changes not detected by salpingoscopy. Fallopian tubes with severe disease were diagnosed by both methods. Transmission electron microscopy of histologically abnormal tubes showed flattening of the epithelium with markedly reduced ciliary distribution, degenerating secretory epithelial cells with large intracellular vacuoles, and swollen nuclei containing sparse chromatin. Our results indicate that salpingoscopic observations are consistent with histologic findings when endotubal disease is severe. However, moderate pathologic changes as documented by light microscopy and transmission electron microscopy were frequently not diagnosed salpingoscopically, even with magnification.
The purpose of this study was to analyze factors associated with multiple gestations in IVF-ET. Twenty-seven multiple gestations conceived following IVF-ET resulted in the delivery of 20 sets of twins and three sets of triplets. One quadruplet pregnancy was terminated due to heavy bleeding. There were four "vanishing sacs," two of which resulted in a twin pregnancy and two in singletons. These were compared to 88 singleton IVF-ET gestations. The only significant difference found was the higher numbers of embryos transferred in the multiple gestation group. No difference was found between the two groups in diagnosis, stimulation protocol, estradiol, response, number of eggs, fertilization, and cleavage rate. Maternal age was younger in the multiple-gestation group, though not statistically significant. It is thus suggested that limitation of the number of embryos transferred is the only means to reduce the incidence of multiple gestations in IVF-ET.
This study was undertaken to examine the predictive value of low estradiol (E2) after 5 days of human menopausal gonadotropin (hMG) stimulation response to therapy in that cycle. We further examined whether the outcome of such cycles can be improved by increasing the hMG dose. When 18 cycles in which day 8 E2 was less than or equal to 50 pg/mL were compared with 48 cycles with corresponding E2 levels of 51 to 150 pg/mL, the former showed a significantly worse response to subsequent hMG therapy. To determine the effect of an increase in hMG dose we studied 48 cycles with day 8 E2 of 51 to 150 pg/mL. In 32 cycles hMG dose was increased from three to a mean of five ampules a day, after 5 days of therapy. In 16 cycles it was kept constant at three ampules per day. Although a tendency towards lower fertilization rate was observed in the higher hMG groups, no significant differences were observed in the results between the two groups. We thus conclude that very low E2 levels after 5 days of gonadotropin therapy are predictive of low response in that cycle, and that in cycles with day 8 E2 of 51 to 150 pg/mL, increasing the dosage of hMG on day 8 and beyond does not alter the course of the cycle.
Femoral neuropathy has been reported to occur after abdominal hysterectomies and has been related to nerve compression by abdominal wound retractors. We report a case of a 35-year-old woman with infertility who developed unilateral femoral nerve palsy after laparoscopy and hysteroscopy. This rare complication, secondary to extreme flexion, abduction and lateral rotation of the hip joint, can be prevented by careful preoperative patient positioning.
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Clomiphene citrate (CC) has known antifecundity effects in animal models. To help define the site of action of this effect, we studied the direct effect of CC on endometrial receptivity by transferring embryos to hormonally prepared prepubertal mice. Prepubertal mice were begun on one of four blinded hormonal preparations consisting of two consecutive 3-day periods of daily injections: oil vehicle, oil-progesterone (P), estradiol (E2)-P, or CC-P. Blastocysts, which had not been exposed to CC, were then surgically transferred to these prepubertal recipients. Fourteen days after embryo transfer, implantations and term pregnancies were counted at necropsy. In this model, CC demonstrated no estrogen agonist effect, and had a significant adverse effect on endometrial receptivity. CC appeared to lower fecundity by a direct endometrial effect.
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Müllerian duct derivatives were identified in an infertile adult male patient who had long-standing azoospermia and was operated on for inguinal hernia. Persistent müllerian duct syndrome is reviewed, with special emphasis on the pathophysiologic and surgical considerations involved in the treatment of this abnormality.
Twenty-five cases of Crohn's disease confined to the appendix were reported in eight hospitals in Israel during a 15-year period. Review of the histologic slides confirmed the diagnosis in 22 cases. Re-evaluation of these 22 patients included physical examination and radiologic studies of the small and large bowel. Rectosigmoidoscopy was performed in 16 patients. Signs and symptoms of Crohn's disease at other sites in the gastrointestinal tract did not occur during follow-up periods of two to 15 years (mean, 6.4 years) after appendectomy. This study and a review of the literature indicate that in most cases (93 per cent) Crohn's disease initially limited to the appendix is not a predictor of subsequent involvement of another portion of the bowel. It is concluded that the so-called Crohn's disease isolated to the appendix is a form of chronic granulomatous and follicular appendicitis of unknown etiology that is unrelated nosologically in the majority of the cases to Crohn's disease proper.
Dynamic computerized heart studies using 99Tc-DTPA demonstrated a joined heart in conjoined thoracopagus twins. In the case presented, the electrocardiogram, dynamic radioactive study, and the cardiac catheterization all gave basically the same results and correlated well with the postmortem examination. The dynamic study is presented in detail, stressing its advantage as a noninvasive and reliable procedure in the primary cardiac assessment of conjoined twins.
A 16-year-old girl with a history of achalasia of the lower esophagus was investigated for progressive constipation since the age of five years. Normal ganglion cells of the Meissner's plexus were found in a mucosal rectal biopsy. Manometric studies showed absence of the normal rectosphincteric relaxation reflex. A long posterior rectal myectomy was performed in which no ganglion cells were found between the muscular layers. The patient underwent a rectosigmoid resection with a low anastomosis according to Duhamel. In the resected bowel, a normal Meissner's plexus was again found while marked hypoganglionosis of the myenteric plexus was evident. Intranuclear inclusion bodies in Schwann cells and scattered inflammatory cells were noteworthy. This case may be an example of an acquired hypoganglionosis localized to the myenteric plexus.
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