Biomedical subjects
Publications and source records attributed to E J Margalioth.
Eighty-two men underwent spermatic vein ligation as treatment for infertility. The resultant mean rates of 22% for semen improvement and 28% for pregnancy justify the surgical approach in selected cases of male infertility.
Evolutionarily conserved antigens are present on spermatozoa of several mammalian species. We tested sera from infertile men and women containing antisperm antibodies (ASAs) for their reactivity with FA-1, an antigen known to be present on murine and human spermatozoa. Fifty percent of male sera and 63% of female sera contained anti-FA-1 antibodies, as judged by enzyme linked immunosorbent assay (ELISA). Fourteen percent of male sera and 50% of female sera were also shown to possess ASAs reactive with living mouse spermatozoa, and murine in vitro fertilization was inhibited by human antibodies. These results suggest that the transfer of immunoglobulins from human sera to spermatozoa of other species may provide a model to study how ASAs effect sperm function.
Three hundred sixty-nine infertile couples were followed for 2 to 5 years in a study designed to determine the clinical long-term predictive value of the zona-free hamster ova sperm penetration assay (SPA). Semen analysis (SA), SPA, and a full infertility workup were done in all cases, and only couples in whom the female had no evident cause of infertility were included in the study. During the follow-up period, 106 couples (29%) achieved a pregnancy. Sixteen percent of 131 men who had an SPA of 0%, 23% of 120 men with 1% to 19%, and 48% of 118 men who had a penetration of greater than 19% impregnated their wives 2 to 5 years after the assays. Significant difference in fertility prognosis was found between those who had an SPA greater than 19% and those with an SPA less than 20% (48% versus 20%). Sperm penetration assay greater than 19% was predictive of higher pregnancy rates in both oligospermic (41% versus 17%) and unexplained infertile couples (52% versus 24%). The specificity and positive predictive values of the SPA were higher than those of the SA (77% versus 57% and 48% versus 37%). These findings emphasize the value and importance of the SPA in determining the long-term fertility potential of men.
This study was undertaken to clarify discriminative roles of multiple epidemiologic, hormonal, and biophysical variables for causation of ovarian hyperstimulation syndrome. Three hundred ninety-six patients with anovulatory infertility had ovulation induction with human menopausal gonadotropin throughout 1822 treatment cycles; 54 cycles (3%) were complicated by ovarian hyperstimulation syndrome. Early follicular serum estradiol and prolactin levels were higher in this group than in controls: 75.5 versus 46.2 pg/ml and 18.5 versus 11.7 ng/ml, respectively (p less than 0.01). On the day of human chorionic gonadotropin administration (day 0) the mean serum estradiol level was 1047 +/- 381 in the group with ovarian hyperstimulation syndrome and 719 +/- 339 pg/ml in controls (p less than 0.0001). In all follicular sizes and in all grades of ovarian hyperstimulation syndrome there was a tendency for more recruited follicles, with significantly more small follicles (12 to 14 mm) present on day 0 in all grades of ovarian hyperstimulation syndrome than in controls. Stepwise logistic regression performed on 22 variables identified a high-risk group for this syndrome; the major features are illustrated by young, lean patients who, after relatively few ampules of human menopausal gonadotropin, develop high estradiol levels and multiple small follicles.
The hormonal factors responsible for variation in sperm penetration rates of zona-free hamster ova caused by the use of human sera were investigated. Sera obtained at different times in the menstrual cycle, 17-beta estradiol (E2), or progesterone (P) was added to Biggers Whitten and Whittingham (BWW) medium used for the sperm penetration assay. Luteal phase sera enhanced egg penetration significantly when compared with either follicular or preovulatory sera (48.8% versus 23% and 25%; P less than 0.01). E2 at concentrations of 2 pg/ml to 2 X 10(6) pg/ml had no effect on sperm motility or egg penetration. Addition of P to control media at final concentrations of 0.5 to 50 ng/ml caused a significant elevation of egg penetration (68% to 91% to 96%; P less than 0.01) without affecting sperm motility. Since P has been shown to have a direct effect on plasma membranes and to bind to spermatozoan plasma membrane, the authors propose that P could have a physiologic role during capacitation or sperm egg interaction in vivo.
The concurrence of dermatomyositis and ovarian carcinoma deserves special attention owing to the gravity of its prognosis. Until now, only scattered case reports on women suffering from this disease combination had been published. In this paper the information available in the literature on 28 women afflicted with these diseases is collated. In addition, two such patients treated in our hospital are described in detail. The review highlights the various aspects of this disease combination, emphasizing the quadrupled incidence, advanced stage and uniform epithelial origin of the malignancy as compared with that in the general female population with ovarian carcinoma. The value of a meticulous gynecologic evaluation was proven in one of our patients with dermatomyositis; in her, ovarian carcinoma was detected in its early phase.
A clomiphene citrate (CC) challenge test was used to prospectively assess future fertility potential in 51 women aged 35 or more with unexplained infertility. Baseline (day 2-3 of the menstrual cycle) and response levels (day 9-11) of follicle stimulating hormone (FSH), luteinising hormone (LH), and 17-beta oestradiol were measured before and after administration of 100 mg clomiphene on days 5-9 of the menstrual cycle. Although all the women had a normal baseline FSH, 18 had an exaggerated FSH response of 26 mIU/ml or more (over 2 standard deviations above control values); this was regarded as a diminished ovarian reserve (DOR). In the DOR group mean response FSH was 38.9 mIU/ml (SD 13.8) and in 33 women with adequate ovarian reserve (AOR) it was 11.5 (4.9) mIU/ml (p less than 0.0001). In the DOR group 1 of 18 patients and in the AOR group 14 of 33 (42%) conceived (p less than 0.05). It is suggested that despite apparently normal ovulatory cycles, the DOR group has a compromised follicular apparatus. Disparity between normal oestradiol secretory capacity of the granulosa and diminished capacity to secrete inhibin could explain the inappropriately high FSH levels in response to the CC challenge.
Fifty-eight follicular fluids (FF) were obtained from 18 women undergoing in vitro fertilization (IVF). Follicular development was induced by human menopausal gonadotropin (hMG) and follicular aspiration was performed 36 hr after an ovulatory dose of human chorionic gonadotropin (hCG). Two stages of oocyte-corona-cumulus complexes (OCCCs) morphological maturation was identified in this population: intermediate and mature. FF from which intermediate and mature OCCCs were obtained did not differ in 17 beta-estradiol (E2), progesterone (P), and cholesterol levels. Fifty OCCCs were fertilized and eight were not fertilized. No difference was found in E2, P, and cholesterol levels in those two populations of OCCCs. Forty hours after insemination 50% of the oocytes were at the two-cell stage and 50% were at the three-cell stage. Steroids and cholesterol levels did not differ in FF from which those two groups of embryos originated. A direct correlation was found among the levels of cholesterol, E2, and P in the FF. An inverted ratio of high-density lipoprotein (HDL) to low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) was found in FF compared to serum in 10 women. It is concluded that FF cholesterol levels have no value in predicting follicular maturation.
Serum copper level was determined before operation in 179 patients with various histologically proved gynecologic tumors: malignant, benign, or metastases to the ovary. Serum copper level was significantly higher (p less than 0.01) in all groups of patients with cancer and in the benign group when compared with control subjects. Serum copper level correlated well with stage of cancer disease (r = 0.70 to 0.79) except for ovarian carcinoma, in which serum copper level was already significantly elevated in Stages I and II. The sensitivity of serum copper level greater than 150 micrograms/dl in detecting malignancy was 87% to 100% in late cancer stages in all malignancies. Our data imply that the addition of serum copper level determination to other screening tests could increase their sensitivity.
The value of multiple parameters in the prediction of fertile cycles was prospectively evaluated in 52 menotropin-induced cycles. The periovulatory pattern of estradiol (E2) was found to correlate with conceptional cycles. E2 levels greater than 500 pg/ml on the day of human chorionic gonadotropin administration (day 0) with a further increase on day +1 (high ascending pattern--A1) were found to have a 51% predictive value for fertile cycles. Twelve of the 17 fertile cycles had an A1, type of response (71%), whereas the overall incidence of an A1 pattern was 42% (22 of 52). No pregnancies have occurred with preovulatory follicles less than or equal to 14 mm in diameter. The number of preovulatory follicles, E2 level on day 0, and midluteal progesterone had no predictive value for fertile cycles.
Plasma renin activity (PRA) and aldosterone were measured throughout the luteal phase in 21 anovulatory patients who developed ovarian hyperstimulation syndrome (OHSS) during menotropin induction of ovulation. The pattern of PRA in hyperstimulated cycles is characterized by a midluteal peak, which declines to normal in the late luteal phase in nonconceptual cycles, whereas a sustained elevation of PRA occurs in conceptual cycles. Midluteal PRA is significantly (P less than 0.001) elevated in patients with OHSS compared with controls. In the mild form of the disease, the median of PRA is 7.5 (range 6 to 11) ng angiotensin I (AI)/ml/hr, significantly higher than the median for controls, 3.0 ng AI/ml/hr (range, 1.4 to 5). In moderate OHSS, PRA was 24.5 (range, 10 to 40) ng AI/ml/hr, whereas, in the severe form of OHSS, PRA was 55.0 (range, 29 to 95) ng AI/ml/hr. A significant correlation (P less than 0.05) was demonstrated between PRA and either progesterone or 17 beta estradiol (E2). The renin-angiotensin cascade is implicated in new vessel formation. Angiogenesis itself is associated with a rapid increase in capillary permeability. The recent demonstration of high plasma renin-like activity in human follicular fluid and the present observation of high PRA in patients with OHSS may imply that the locally active renin angiotensin system, through induction of new vessel formation and increase in capillary permeability, may have a casual relationship to the ovarian enlargement and extracellular fluid accumulation that are the hallmarks of OHSS.
In eight women with ovarian failure, we induced histologically normal endometrial function during a preparatory cycle consisting of sequential administration of estrogen and progesterone. During a subsequent cycle, endometrial stimulation was synchronized with surrogate-embryo transfer performed on days 16 to 21. Among the eight women, two pregnancies were established by embryo transfer on days 18 and 19. In both women, ovarian tissue was absent, and these patients therefore serve as an in vivo model for the isolated effects of estrogen and progesterone on implantation and maintenance of pregnancy. Treatment with exogenous estrogen was mandatory up to the 11th week of gestation, and treatment with progesterone until the 18th to 22nd weeks. We conclude that it is biologically feasible to simulate the essential hormonal and endometrial milieu of a fertile menstrual cycle and early gestation solely by the administration of estrogen and progesterone. Days 18 to 19 of the cycle are recommended for successful embryo implantation with this treatment program.
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The association between in vitro fertilization (IVF) and the zona-free hamster egg sperm penetration assay (SPA) was studied in 134 couples. The indications for IVF were tubal disease in 82 couples, unexplained infertility in 23, male infertility in 10, and combined mechanical and male factors in 19. In general, a positive SPA was a good predictor of subsequent IVF (91 of 107 couples). Specificity (number of couples with fertilization in vitro divided by the number of couples with a positive SPA times 100) was 94% for tubal infertility, 76% for unexplained infertility, and 46% for male infertility. A negative SPA predicted an overall fertilization failure of 78% (21 of 27 couples). Sensitivity of the test (number of couples with IVF failure divided by the number of couples with a negative SPA times 100) was 100% for tubal and unexplained infertility but only 63% for male infertility. The high predictive value of the SPA for subsequent IVF outcome in tubal infertility and unexplained infertility warrants its routine use for prescreening in IVF programs. Because of the lack of association between SPA and IVF in oligoasthenospermia, the bioassay should not be relied upon for predicting IVF outcome in male subfertility. The overall high association between the animal model and human IVF reinforces the use of the SPA for both basic research and clinical decision-making.
This work was undertaken for evaluation of the value of endometrial thickness as an early predictor for the success of in vitro fertilization (IVF). Endometrial changes were evaluated ultrasonographically in 47 women undergoing IVF. A high-dose gonadotropin protocol was used for induction of multiple follicular development. Thirty-seven women did not conceive following the procedure (group I), and 10 conceived (group II). Ultrasonographic endometrial measurements were performed repeatedly throughout the cycle. Serum 17 beta-estradiol and progesterone levels were evaluated concomitantly. Three consecutive growth patterns of the endometrium were observed. The first was a rapid one with a daily growth rate of about 0.5 mm from approximately 9 mm on day -3 to 12 mm on day +2 (day 0 being the day of human chorionic gonadotropin administration). The second phase, following follicular aspiration, showed a decrease in growth rate to about 0.1 mm per day until day +11, when a thickness of about 13 mm was measured. In group I growth was arrested from day +11 until menstruation, whereas in group II an accelerated growth rate of about 0.4 mm per day could be demonstrated from day +14 onward. Endometrial growth did not correlate with serum estradiol or progesterone levels. No conception occurred with an endometrial thickness below 13 mm on day +11. It is concluded that endometrial thickness follows a distinct pattern of growth in human menopausal gonadotropin-induced cycles and does not correlate with serum sex hormones.(ABSTRACT TRUNCATED AT 250 WORDS)
Ultrasonically guided oocyte collection gradually replaces laparoscopy in many in vitro fertilization (IVF) centers. In the present study we compare the efficacy of both methods in our IVF program. One hundred twenty patients were prospectively randomized into two groups. Sixty women underwent oocyte collection during laparoscopy under general anesthesia, and 60 women under ultrasound guidance with local anesthesia. Superovulation was induced with human menopausal gonadotropin/human chorionic gonadotropin. For the oocyte collection a cannula with a trocar was used for single percutaneous puncture, through which both ovaries could be reached by the aspiration needle. The number of aspirated oocytes and transferred embryos was higher in the laparoscopy group as compared with the ultrasound group (5.3 versus 4.0 per woman and 3.0 versus 2.3 per woman, respectively); but the clinical pregnancy rate per cycle was similar in both groups (12.5% versus 14.5%). Ultrasound aspiration seems to be as effective as laparoscopy in terms of oocyte retrieval and conception rates. Because the procedure is simple and inexpensive, we believe that it may replace laparoscopy as a method for oocyte collection in most patients who undergo IVF.
Three women presented with acute primary herpetic gingivostomatitis during the first half of their pregnancy. Herpes simplex virus (HSV) was isolated by culture from the buccal lesions in two cases, and a serological confirmation of primary HSV infection was evident in the third case. One fetus, delivered during the second trimester of pregnancy, had a central nervous system anomaly, which was probably not related to the infection. The placenta exhibited mild diffuse deciduitis and focal villitis. The other two fetuses were normal and born at term. Microscopic examination of the placentas and membranes disclosed deciduitis and basal placentitis in one, which may have been caused by the herpes virus. The literature on intrauterine infection with HSV is reviewed, focusing on the significance of Type I virus as a possible teratogen. At present, there seems to be insufficient evidence to indicate pregnancy interruption following nongenital primary HSV infection in early pregnancy.
Serum copper levels (SCL) were determined before any diagnostic procedure was performed or treatment given in 40 women admitted for the investigation of a pelvic mass and, later, in those patients with ovarian carcinoma after chemotherapy and before a second-look operation was performed. Patients with ovarian carcinoma were found to have significantly higher SCL than patients with benign ovarian lesions. A SCL of 150 micrograms/dl clearly separated patients with a pelvic mass on the basis of ovarian carcinoma and those with benign noninflammatory pelvic lesions. The same SCL of 150 micrograms/dl separated patients with ovarian carcinoma that responded to chemotherapy and those with residual disease. It is suggested that SCL be included as a member of the screening panel of biologic tumor markers in general and in ovarian carcinoma in particular.