The use of follicle-stimulating hormone for controlled ovarian hyperstimulation in in vitro fertilization.
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Cell Division↗
Biomedical subjects
D Navot
Publications and source records attributed to D Navot.
Indication of selective growth of human endometrial epithelial cells on extracellular matrix.
The culturing of human endometrium in conventional plastic dishes and media is only partially successful, mainly because a growth of a heterogeneous population of cells is achieved. Naturally produced extracellular matrix closely resembles the subepithelial basement membrane and seems to affect both growth and differentiation of cells. These qualities of the extracellular matrix (ECM) were applied for obtaining endometrial epithelial cultures. Endometrial tissue specimens were plated after slicing on ECM-coated dishes and kept for up to 8 d. The growth of a confluent homogeneous tissue composed of polygonal epithelial-like cells was demonstrated. To further characterize these cells, cultures were examined by scanning electron microscopy and transmission electron microscopy. Scanning electron microscopy revealed flattened polygonal cells covered with microvilli, among which ciliated cells were observed. By transmission electron microscopy the cells were seen as a monolayer, with some cells overlapping, closely adherent to the matrix. Microvilli, as well as intracellular vacuoles and glycogen granules were observed. Cell type specific cytoskeletal markers were demonstrated by antibodies to intermediate filament proteins (keratin and epithelial membrane antigen). Taken together, the morphologic and immunohistochemical studies indicate that a selective growth of the epithelial component of endometrial tissue was obtained after plating unprocessed endometrial tissue fragments on ECM-coated culture dishes.
Adult↗
Risk factors and prognostic variables in the ovarian hyperstimulation syndrome.
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.
Adult↗
Concomitant gonadotropin-releasing hormone agonist and menotropin treatment for the synchronized induction of multiple follicles.
In an effort to overcome possible interference by endogenous gonadotropin-ovarian hormone dynamics, desensitization of the pituitary gonadotropins by a gonadotropin-releasing hormone agonist (GnRHa) was achieved in 12 women with repeatedly failed attempts at multiple follicular stimulation. Eight women were scheduled for in vitro fertilization (IVF) and embryo transfer (ET), and 4 for gamete intrafallopian transfer (GIFT). Stimulation failure was characterized by premature luteinization, poor estradiol (E2) response, or inadequate follicular growth. The agonist was administered by nasal spray 500 to 600 micrograms/day beginning on days 21 to 23 of the menstrual cycle. A rapid desensitization occurred by 7.6 +/- 0.6 days (mean +/- standard error [SE]) following the initial dose. Gonadotropin stimulation was begun when pituitary and ovarian suppression was judged to be adequate. In response to gonadotropin stimulation, a continuous rise of E2 was observed in all patients with a mean of 989 +/- 46 pg/ml on the day of hCG. A cohort of synchronized follicles was recruited and matured. The mean number of growing follicles per patient was significantly higher (P less than 0.0001) in combined therapy than in previously failed cycles (8.0 +/- 0.3 versus 3.2 +/- 0.1). All the patients underwent oocyte retrieval and 94.3% of the harvested oocytes were preovulatory. A high fertilization rate (89.7%) of the inseminated oocytes occurred in IVF patients.
Adult↗
The value of in vitro fertilization for the treatment of unexplained infertility.
In 54 patients referred with the diagnosis of unexplained infertility (UI), the diagnosis was confirmed in 26 (strict UI) (48%). Minimal abnormalities (MA) were found in 19 (35%); 9 (17%) had gross abnormalities and were excluded from analysis. Fifty patients with tubal infertility were randomly assigned to form a control group. Mean age and type of stimulation did not differ in the two groups. Peak follicular estradiol (E2) and terminal follicular E2 patterns were comparable. There was no difference in the mean number of oocytes retrieved per cycle. However, the control group had significantly more preovulatory oocytes: 3.6 +/- 2.0 standard deviations versus 2.8 +/- 2.1 in the overall UI group (strict UI + MA groups) and 2.7 +/- 2.2 in the strict UI group. Significantly more fertilized oocytes per cycle were obtained in the control group (P less than 0.05). The per-cycle and per-embryo transfer (ET) pregnancy rates were 32.4 and 37.3% in the overall UI group and 24 and 24.5% in the control group. The miscarriage rate was 12% in the strict UI group, 22% in the overall UI group, and 25% in the control group. It is concluded that patients with UI constitute a favorable group for in vitro fertilization and ET.
Chorionic Gonadotropin↗
Transdermal estrogen replacement in ovarian failure for ovum donation.
This study examined the efficacy of transdermal estradiol (TE2) replacement versus oral estradiol (OE2) through evaluation of peripheral steroid levels, endometrial morphology, and clinical outcome in six patients with ovarian failure. Patients were begun on sequential E2 and progesterone replacement with transdermal E2 patches. Endometrial biopsies were done on day 21 of the first replacement cycle and day 26 of the second cycle. Controls were 28 cycles on a regular 28-day micronized OE2 protocol. No significant difference was found between E2 levels throughout the cycle of the two respective stimulation protocols, except for days 12 to 14, when the OE2 protocol produced significantly lower E2 than did the TE2 protocol (P less than 0.01). A positive, highly significant correlation was found between estrone (E1) and E2 values in the OE2 group (r = 0.92) (P less than 0.003). During OE2 administration, E1 was significantly higher than E2 (P less than 0.01). E1 was not found to be higher than E2 in the TE2 group, resulting in a significant difference in the E2/E1 ratio of 1.59 +/- 1.6 for TE2 compared with 0.13 +/- .04 for OE2 (P less than 0.05). Early biopsies in patients on TE2 revealed glandular components that were dated as day 18.2 +/- 1.7, while the stroma was dated as day 21.8 +/- 0.8, a statistically significant disparity (P less than 0.01). In patients on OE2, the same significant 3-day glandular/stromal disparity was observed (P less than 0.05). Morphologic evaluation of late biopsy specimens revealed day 25.0 +/- 0.8 and 24.5 +/- 1.5 for TE2 and OE2 groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Cutaneous↗
Spontaneous and pharmacologically induced remissions in patients with premature ovarian failure.
To determine the fertility potential of patients with apparent ovarian failure, a retrospective analysis of 86 ovarian failure patients in the Norfolk oocyte donation program was performed. None of the 23 patients with primary ovarian failure ovulated. Seven of 63 (11.1%) with secondary ovarian failure did ovulate, and three of 63 (4.8%) conceived and delivered normal, healthy infants. Of patients whose etiology for ovarian failure was partial ovarian resection or chemotherapy, the ovulation rate and pregnancy rate were 30.8 and 15.4%, respectively, compared with 5.0 and 1.7%, respectively, for the other patients with secondary ovarian failure. Serum estradiol and FSH obtained during hormone replacement were not predictive of the resumption of normal reproductive functions. Therefore, it is recommended that patients with secondary ovarian failure, especially in the better-prognosis group, be treated with a trial of estradiol replacement and have close monitoring for ovulation before oocyte donation.
Adult↗
Second stage fetal heart rate decelerations in breech deliveries.
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Breech Presentation↗
Oocyte donation. The Norfolk Program.
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Embryo Transfer↗
Prognostic assessment of female fecundity.
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.
Adult↗
Cholesterol and steroid levels in human follicular fluids of human menopausal gonadotropin-induced cycles for in vitro fertilization.
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.
Adult↗
Fryns syndrome: a predictable, lethal pattern of multiple congenital anomalies.
Fryns syndrome is a unique pattern of lethal multiple congenital malformations with variable expression. A family in which all four sibs conformed to Fryns syndrome is detailed and substantiates the criteria for definition of the syndrome; perinatal mortality, hypoplastic lungs, and facial deformities should be highly suggestive of the syndrome. The addition of a strong family history, diaphragmatic hernias, distal limb deformities, and early onset of polyhydramnios with subsequent premature delivery should definitely confirm the diagnosis.
Abnormalities, Multiple↗
The effect of estradiol valerate and allylestrenol on endometrial transformation in hypergonadotropic hypogonadic women.
The effect of estradiol valerate and allylestrenol on the endometrial transformation of five hypergonadotropic hypogonadic women was evaluated. Estradiol valerate was administered throughout the whole induced cycle (28 days), while allylestrenol was added during the second half of the cycle. Endometrial biopsies were performed during allylestrenol treatment and were evaluated histologically. Samples of endometrium were also subjected to one-dimensional SDS electrophoresis. Of ten biopsies performed, only one was interpreted to be in-phase, while the others were dated proliferative (4 biopsies) or showed abortive or out-of-phase secretory transformation. The highest mean serum progesterone level, detected under allylestrenol treatment, was 1.5 ng/ml. Protein electrophoresis demonstrated relative sequential changes in the protein patterns of the 115 kDa and 150 kDa protein bands. It is concluded that allylestrenol, although having gestagen properties, may not be efficient for the induction of an adequate secretory transformation of human endometrium in the absence of ovaries.
Adult↗
Periovulatory 17 beta-estradiol pattern in conceptional and nonconceptional cycles during menotropin treatment of anovulatory infertility.
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.
Anovulation↗
Direct correlation between plasma renin activity and severity of the ovarian hyperstimulation syndrome.
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.
Adult↗
Artificially induced endometrial cycles and establishment of pregnancies in the absence of ovaries.
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.
Adult↗
Correlation between the zona-free hamster egg sperm penetration assay and human in vitro fertilization.
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.
Animals↗
The value of ultrasonographic endometrial measurement in the prediction of pregnancy following in vitro fertilization.
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)
Adult↗